module_id module_title module_path reactome_id scope node_id node_label node_type annoton_id annoton_label function_id function_label participant_ids participant_labels statement reactome_cached reactome_path reactome_display_name reactome_species adrenal_steroidogenesis Adrenal steroidogenesis — cholesterol to corticosteroids and adrenal androgens; STAR/CYP11A1/HSD3B2/CYP17A1/CYP21A2/CYP11B1/CYP11B2 modules/adrenal_steroidogenesis.yaml R-HSA-193048 module_evidence "The androgen branch (CYP17A1 17,20-lyase -> DHEA; HSD3B2 -> androstenedione) follows human Reactome ""Androgen biosynthesis""." yes reactome/R-HSA-193048.md Androgen biosynthesis Homo sapiens adrenal_steroidogenesis Adrenal steroidogenesis — cholesterol to corticosteroids and adrenal androgens; STAR/CYP11A1/HSD3B2/CYP17A1/CYP21A2/CYP11B1/CYP11B2 modules/adrenal_steroidogenesis.yaml R-HSA-193052 activity_evidence hsd3b2_step pregnenolone to progesterone (and 17OH-pregnenolone to 17OH-progesterone; DHEA to androstenedione) REACTION hsd3b2_activity HSD3B2: 3beta-HSD / Delta5-Delta4 isomerase (type 2) GO:0003854 3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity UniProtKB:P26439 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 Pregn-5-ene-3,20-dione isomerizes to progesterone (human Reactome reaction) yes reactome/R-HSA-193052.md Pregn-5-ene-3,20-dione isomerizes to progesterone Homo sapiens adrenal_steroidogenesis Adrenal steroidogenesis — cholesterol to corticosteroids and adrenal androgens; STAR/CYP11A1/HSD3B2/CYP17A1/CYP21A2/CYP11B1/CYP11B2 modules/adrenal_steroidogenesis.yaml R-HSA-193072 activity_evidence cyp17a1_step 17alpha-hydroxylation and 17,20-lyase (to 17OH-steroids and DHEA/androstenedione) REACTION cyp17a1_activity CYP17A1: 17alpha-hydroxylase/17,20-lyase (P450c17) GO:0004508 steroid 17-alpha-monooxygenase activity UniProtKB:P05093 Steroid 17-alpha-hydroxylase/17,20 lyase CYP17A1 17-hydroxylates P4 to 17aHPROG (human Reactome reaction) yes reactome/R-HSA-193072.md CYP17A1 17-hydroxylates P4 to 17aHPROG Homo sapiens adrenal_steroidogenesis Adrenal steroidogenesis — cholesterol to corticosteroids and adrenal androgens; STAR/CYP11A1/HSD3B2/CYP17A1/CYP21A2/CYP11B1/CYP11B2 modules/adrenal_steroidogenesis.yaml R-HSA-193099 activity_evidence cyp17a1_step 17alpha-hydroxylation and 17,20-lyase (to 17OH-steroids and DHEA/androstenedione) REACTION cyp17a1_activity CYP17A1: 17alpha-hydroxylase/17,20-lyase (P450c17) GO:0004508 steroid 17-alpha-monooxygenase activity UniProtKB:P05093 Steroid 17-alpha-hydroxylase/17,20 lyase CYP17A1 cleaves 17aHPROG to ANDST (17,20-lyase; human Reactome reaction) yes reactome/R-HSA-193099.md CYP17A1 cleaves 17aHPROG to ANDST Homo sapiens adrenal_steroidogenesis Adrenal steroidogenesis — cholesterol to corticosteroids and adrenal androgens; STAR/CYP11A1/HSD3B2/CYP17A1/CYP21A2/CYP11B1/CYP11B2 modules/adrenal_steroidogenesis.yaml R-HSA-193101 activity_evidence cyp11a1_step cholesterol to pregnenolone REACTION cyp11a1_activity CYP11A1: cholesterol side-chain cleavage (P450scc) GO:0008386 cholesterol monooxygenase (side-chain-cleaving) activity UniProtKB:P05108 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 cleaves 20a,22b-DHCHOL (human Reactome reaction) yielding pregnenolone yes reactome/R-HSA-193101.md CYP11A1 cleaves 20a,22b-DHCHOL Homo sapiens adrenal_steroidogenesis Adrenal steroidogenesis — cholesterol to corticosteroids and adrenal androgens; STAR/CYP11A1/HSD3B2/CYP17A1/CYP21A2/CYP11B1/CYP11B2 modules/adrenal_steroidogenesis.yaml R-HSA-193964 activity_evidence cyp21a2_step 21-hydroxylation (progesterone to DOC; 17OH-progesterone to 11-deoxycortisol) REACTION cyp21a2_activity CYP21A2: steroid 21-hydroxylase (P450c21) GO:0004509 steroid 21-monooxygenase activity UniProtKB:P08686 Steroid 21-hydroxylase CYP21A2 21-hydroxylates PROG (human Reactome reaction) to 11-deoxycorticosterone yes reactome/R-HSA-193964.md CYP21A2 21-hydroxylates PROG Homo sapiens adrenal_steroidogenesis Adrenal steroidogenesis — cholesterol to corticosteroids and adrenal androgens; STAR/CYP11A1/HSD3B2/CYP17A1/CYP21A2/CYP11B1/CYP11B2 modules/adrenal_steroidogenesis.yaml R-HSA-193965 activity_evidence cyp11b2_step 11-deoxycorticosterone to aldosterone (11beta-/18-hydroxylase/18-oxidase) REACTION cyp11b2_activity CYP11B2: aldosterone synthase (P450c11AS) GO:0047783 corticosterone 18-monooxygenase activity UniProtKB:P19099 Cytochrome P450 11B2, mitochondrial CYP11B2 oxidises 18HCORST to ALDO (human Reactome reaction) yes reactome/R-HSA-193965.md CYP11B2 oxidises 18HCORST to ALDO Homo sapiens adrenal_steroidogenesis Adrenal steroidogenesis — cholesterol to corticosteroids and adrenal androgens; STAR/CYP11A1/HSD3B2/CYP17A1/CYP21A2/CYP11B1/CYP11B2 modules/adrenal_steroidogenesis.yaml R-HSA-193981 activity_evidence cyp21a2_step 21-hydroxylation (progesterone to DOC; 17OH-progesterone to 11-deoxycortisol) REACTION cyp21a2_activity CYP21A2: steroid 21-hydroxylase (P450c21) GO:0004509 steroid 21-monooxygenase activity UniProtKB:P08686 Steroid 21-hydroxylase CYP21A2 oxidises 17HPROG (human Reactome reaction) to 11-deoxycortisol yes reactome/R-HSA-193981.md CYP21A2 oxidises 17HPROG Homo sapiens adrenal_steroidogenesis Adrenal steroidogenesis — cholesterol to corticosteroids and adrenal androgens; STAR/CYP11A1/HSD3B2/CYP17A1/CYP21A2/CYP11B1/CYP11B2 modules/adrenal_steroidogenesis.yaml R-HSA-193993 module_evidence "The mineralocorticoid branch (CYP21A2 -> DOC; CYP11B2 through corticosterone and 18-hydroxycorticosterone to aldosterone) follows human Reactome ""Mineralocorticoid biosynthesis""." yes reactome/R-HSA-193993.md Mineralocorticoid biosynthesis Homo sapiens adrenal_steroidogenesis Adrenal steroidogenesis — cholesterol to corticosteroids and adrenal androgens; STAR/CYP11A1/HSD3B2/CYP17A1/CYP21A2/CYP11B1/CYP11B2 modules/adrenal_steroidogenesis.yaml R-HSA-193995 activity_evidence cyp11b2_step 11-deoxycorticosterone to aldosterone (11beta-/18-hydroxylase/18-oxidase) REACTION cyp11b2_activity CYP11B2: aldosterone synthase (P450c11AS) GO:0047783 corticosterone 18-monooxygenase activity UniProtKB:P19099 Cytochrome P450 11B2, mitochondrial CYP11B2 18-hydroxylates CORST to 18HCORST (human Reactome reaction) yes reactome/R-HSA-193995.md CYP11B2 18-hydroxylates CORST to 18HCORST Homo sapiens adrenal_steroidogenesis Adrenal steroidogenesis — cholesterol to corticosteroids and adrenal androgens; STAR/CYP11A1/HSD3B2/CYP17A1/CYP21A2/CYP11B1/CYP11B2 modules/adrenal_steroidogenesis.yaml R-HSA-193997 activity_evidence cyp11b1_step 11-deoxycortisol to cortisol REACTION cyp11b1_activity CYP11B1: 11beta-hydroxylase (P450c11beta) GO:0004507 steroid 11-beta-monooxygenase activity UniProtKB:P15538 Cytochrome P450 11B1, mitochondrial CYP11B1 oxidises 11DCORT (human Reactome reaction) to cortisol yes reactome/R-HSA-193997.md CYP11B1 oxidises 11DCORT Homo sapiens adrenal_steroidogenesis Adrenal steroidogenesis — cholesterol to corticosteroids and adrenal androgens; STAR/CYP11A1/HSD3B2/CYP17A1/CYP21A2/CYP11B1/CYP11B2 modules/adrenal_steroidogenesis.yaml R-HSA-194002 module_evidence "The glucocorticoid branch (CYP17A1 17-hydroxylation -> CYP21A2 21-hydroxylation -> CYP11B1 11beta-hydroxylation to cortisol) follows human Reactome ""Glucocorticoid biosynthesis""." yes reactome/R-HSA-194002.md Glucocorticoid biosynthesis Homo sapiens adrenal_steroidogenesis Adrenal steroidogenesis — cholesterol to corticosteroids and adrenal androgens; STAR/CYP11A1/HSD3B2/CYP17A1/CYP21A2/CYP11B1/CYP11B2 modules/adrenal_steroidogenesis.yaml R-HSA-196108 module_evidence "The cholesterol-to-pregnenolone entry (STAR translocation + CYP11A1 side-chain cleavage) follows the human Reactome ""Pregnenolone biosynthesis"" reactions R-HSA-196126/193101." yes reactome/R-HSA-196108.md Pregnenolone biosynthesis Homo sapiens adrenal_steroidogenesis Adrenal steroidogenesis — cholesterol to corticosteroids and adrenal androgens; STAR/CYP11A1/HSD3B2/CYP17A1/CYP21A2/CYP11B1/CYP11B2 modules/adrenal_steroidogenesis.yaml R-HSA-196126 activity_evidence star_step cholesterol translocation to the inner mitochondrial membrane REACTION star_activity STAR: steroidogenic acute regulatory protein GO:0120020 cholesterol transfer activity UniProtKB:P49675 Steroidogenic acute regulatory protein, mitochondrial STAR mediates CHOL translocation from cytosol to mitochondrial intermembrane space (human Reactome reaction) yes reactome/R-HSA-196126.md STAR mediates CHOL translocation from cytosol to mitochondrial intermembrane space Homo sapiens bile_acid_synthesis_ring_modification Bile acid synthesis I — ring modification (cholesterol -> 5-beta-cholestane intermediates); CYP7A1/CYP7B1/HSD3B7/AKR1D1 modules/bile_acid_synthesis_ring_modification.yaml R-HSA-192033 activity_evidence akr1d1_step 7-alpha-hydroxy-4-cholesten-3-one to 5-beta-cholestan-7-alpha-ol-3-one REACTION akr1d1_activity AKR1D1: steroid 5-beta-reductase GO:0047787 Delta4-3-oxosteroid 5beta-reductase activity UniProtKB:P51857 Aldo-keto reductase family 1 member D1 4-cholesten-7alpha-ol-3-one is reduced to 5beta-cholestan-7alpha-ol... (human Reactome reaction) yes reactome/R-HSA-192033.md 4-cholesten-7alpha-ol-3-one is reduced to 5beta-cholestan-7alpha-ol-3-one Homo sapiens bile_acid_synthesis_ring_modification Bile acid synthesis I — ring modification (cholesterol -> 5-beta-cholestane intermediates); CYP7A1/CYP7B1/HSD3B7/AKR1D1 modules/bile_acid_synthesis_ring_modification.yaml R-HSA-192051 activity_evidence cyp7a1_step cholesterol to 7-alpha-hydroxycholesterol REACTION cyp7a1_activity CYP7A1: cholesterol 7-alpha-hydroxylase GO:0008123 cholesterol 7-alpha-monooxygenase activity UniProtKB:P22680 Cholesterol 7-alpha-monooxygenase CYP7A1 7-hydroxylates CHOL (human Reactome reaction) yes reactome/R-HSA-192051.md CYP7A1 7-hydroxylates CHOL Homo sapiens bile_acid_synthesis_ring_modification Bile acid synthesis I — ring modification (cholesterol -> 5-beta-cholestane intermediates); CYP7A1/CYP7B1/HSD3B7/AKR1D1 modules/bile_acid_synthesis_ring_modification.yaml R-HSA-192065 activity_evidence cyp7b1_step 25-/27-hydroxycholesterol to 7-alpha,X-dihydroxycholesterol REACTION cyp7b1_activity CYP7B1: oxysterol 7-alpha-hydroxylase GO:0008396 oxysterol 7-alpha-hydroxylase activity UniProtKB:O75881 25-hydroxycholesterol 7-alpha-hydroxylase CYP7B1 7-hydroxylates 25OH-CHOL (human Reactome reaction) yes reactome/R-HSA-192065.md CYP7B1 7-hydroxylates 25OH-CHOL Homo sapiens bile_acid_synthesis_ring_modification Bile acid synthesis I — ring modification (cholesterol -> 5-beta-cholestane intermediates); CYP7A1/CYP7B1/HSD3B7/AKR1D1 modules/bile_acid_synthesis_ring_modification.yaml R-HSA-192097 activity_evidence hsd3b7_step 7-alpha-hydroxycholesterol to 7-alpha-hydroxy-4-cholesten-3-one REACTION hsd3b7_activity HSD3B7: 3-beta-hydroxy-Delta5-C27-steroid dehydrogenase GO:0003854 3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity UniProtKB:Q9H2F3 3 beta-hydroxysteroid dehydrogenase type 7 7alpha-hydroxycholesterol is oxidized and isomerized to 4-cholesten... (human Reactome reaction) yes reactome/R-HSA-192097.md 7alpha-hydroxycholesterol is oxidized and isomerized to 4-cholesten-7alpha-ol-3-one Homo sapiens bile_acid_synthesis_ring_modification Bile acid synthesis I — ring modification (cholesterol -> 5-beta-cholestane intermediates); CYP7A1/CYP7B1/HSD3B7/AKR1D1 modules/bile_acid_synthesis_ring_modification.yaml R-HSA-192105 module_evidence Reactions follow the human Reactome bile-acid-synthesis reactions R-HSA-192051 (CYP7A1), R-HSA-192065 (CYP7B1), R-HSA-192097 (HSD3B7) and R-HSA-192033 (AKR1D1). yes reactome/R-HSA-192105.md Synthesis of bile acids and bile salts Homo sapiens bile_acid_synthesis_sidechain_conjugation Bile acid synthesis II — side-chain oxidation, peroxisomal shortening and amino-acid conjugation; CYP27A1/AMACR/ACOX2/SLC27A5/BAAT modules/bile_acid_synthesis_sidechain_conjugation.yaml R-HSA-159425 activity_evidence slc27a5_step cholate + CoA + ATP to choloyl-CoA REACTION slc27a5_activity SLC27A5: bile acyl-CoA synthetase (cholate-CoA ligase) GO:0047747 cholate-CoA ligase activity UniProtKB:Q9Y2P5 Bile acyl-CoA synthetase Cytosolic cholate and chenodeoxycholate are conjugated with CoA (human Reactome reaction) yes reactome/R-HSA-159425.md Cytosolic cholate and chenodeoxycholate are conjugated with Coenzyme A (SLC27A5 BACS) Homo sapiens bile_acid_synthesis_sidechain_conjugation Bile acid synthesis II — side-chain oxidation, peroxisomal shortening and amino-acid conjugation; CYP27A1/AMACR/ACOX2/SLC27A5/BAAT modules/bile_acid_synthesis_sidechain_conjugation.yaml R-HSA-191999 activity_evidence cyp27a1_step sterol side-chain 27-hydroxylation/oxidation to THCA/DHCA REACTION cyp27a1_activity CYP27A1: sterol 27-hydroxylase GO:0047748 cholestanetetraol 26-dehydrogenase activity UniProtKB:Q02318 Sterol 26-hydroxylase, mitochondrial CYP27A1 27-hydroxylates 5bCHOL3a,7a,12a-triol (human Reactome reaction) yes reactome/R-HSA-191999.md CYP27A1 27-hydroxylates 5bCHOL3a,7a,12a-triol Homo sapiens bile_acid_synthesis_sidechain_conjugation Bile acid synthesis II — side-chain oxidation, peroxisomal shortening and amino-acid conjugation; CYP27A1/AMACR/ACOX2/SLC27A5/BAAT modules/bile_acid_synthesis_sidechain_conjugation.yaml R-HSA-192056 activity_evidence amacr_step (25R)-THCA-CoA to (25S)-THCA-CoA REACTION amacr_activity AMACR: alpha-methylacyl-CoA racemase GO:0008111 alpha-methylacyl-CoA racemase activity UniProtKB:Q9UHK6 Alpha-methylacyl-CoA racemase Isomerization of 25(R) THCA-CoA to 25(S) THCA-CoA (human Reactome reaction) yes reactome/R-HSA-192056.md Isomerization of 25(R) THCA-CoA to 25(S) THCA-CoA Homo sapiens bile_acid_synthesis_sidechain_conjugation Bile acid synthesis II — side-chain oxidation, peroxisomal shortening and amino-acid conjugation; CYP27A1/AMACR/ACOX2/SLC27A5/BAAT modules/bile_acid_synthesis_sidechain_conjugation.yaml R-HSA-192312 activity_evidence baat_step choloyl-CoA + glycine/taurine to glyco-/tauro-cholate REACTION baat_activity BAAT: bile acid-CoA:amino acid N-acyltransferase GO:0047963 glycine N-choloyltransferase activity UniProtKB:Q14032 Bile acid-CoA:amino acid N-acyltransferase Choloyl CoA reacts with glycine or taurine to form glycocholate or taurocholate (human Reactome reaction) yes reactome/R-HSA-192312.md Choloyl CoA reacts with glycine or taurine to form glycocholate or taurocholate Homo sapiens bile_acid_synthesis_sidechain_conjugation Bile acid synthesis II — side-chain oxidation, peroxisomal shortening and amino-acid conjugation; CYP27A1/AMACR/ACOX2/SLC27A5/BAAT modules/bile_acid_synthesis_sidechain_conjugation.yaml R-HSA-192335 activity_evidence acox2_step (25S)-THCA-CoA to 24-ene-THCA-CoA (leading to choloyl-CoA) REACTION acox2_activity ACOX2: branched-chain acyl-CoA oxidase GO:0033791 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoyl-CoA 24-hydroxylase activity UniProtKB:Q99424 Peroxisomal acyl-coenzyme A oxidase 2 25(S) THCA-CoA is dehydrogenated to 3alpha,7alpha,12alpha-trihydroxy-cholestenoyl-CoA (human Reactome reaction) yes reactome/R-HSA-192335.md 25(S) THCA-CoA is dehydrogenated to 3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-enoyl-CoA (THCA-CoA) Homo sapiens bile_acid_synthesis_sidechain_conjugation Bile acid synthesis II — side-chain oxidation, peroxisomal shortening and amino-acid conjugation; CYP27A1/AMACR/ACOX2/SLC27A5/BAAT modules/bile_acid_synthesis_sidechain_conjugation.yaml R-HSA-193368 module_evidence "Step order, intermediates and reaction stoichiometries follow the human Reactome ""Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol"" sub-pathway, including the side-chain-oxidation and conjugation reactions cited on each node." yes reactome/R-HSA-193368.md Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol Homo sapiens biotin_cycle Biotin cycle — holocarboxylase synthetase and biotinidase (multiple carboxylase deficiency) modules/biotin_cycle.yaml R-HSA-196780 module_evidence "Reactions follow the human Reactome ""Biotin transport and metabolism"" pathway (R-HSA-196780): HLCS biotinylation of the apo-carboxylases (R-HSA-2993447, R-HSA-2993799, ...) and BTD hydrolysis of biocytin (R-HSA-3076905)." yes reactome/R-HSA-196780.md Biotin transport and metabolism Homo sapiens biotin_cycle Biotin cycle — holocarboxylase synthetase and biotinidase (multiple carboxylase deficiency) modules/biotin_cycle.yaml R-HSA-2993447 activity_evidence hlcs_step apo-carboxylase + biotin + ATP to holo-carboxylase (biotinylated) + AMP + PPi REACTION hlcs_activity HLCS: holocarboxylase synthetase (biotin-protein ligase) GO:0004077 biotin--[biotin carboxyl-carrier protein] ligase activity UniProtKB:P50747 Biotin--protein ligase HLCS biotinylates 6x(PCCA:PCCB) (human Reactome reaction) no biotin_cycle Biotin cycle — holocarboxylase synthetase and biotinidase (multiple carboxylase deficiency) modules/biotin_cycle.yaml R-HSA-3076905 activity_evidence btd_step biocytin (biotinyl-lysine) + H2O to biotin + L-lysine REACTION btd_activity BTD: biotinidase GO:0047708 biotinidase activity UniProtKB:P43251 Biotinidase Extracellular BTD hydrolyses BCTN (human Reactome reaction) no branched_chain_amino_acid_catabolism Branched-chain amino acid (BCAA) catabolism — transamination and the BCKDH complex modules/branched_chain_amino_acid_catabolism.yaml R-HSA-70724 activity_evidence bcat2_step BCAA + 2-oxoglutarate to branched-chain 2-oxo acid + L-glutamate REACTION bcat2_activity BCAT2: branched-chain aminotransferase (mitochondrial) GO:0004084 branched-chain-amino-acid:2-oxoglutarate transaminase activity UniProtKB:O15382|UniProtKB:P54687 Branched-chain-amino-acid aminotransferase, mitochondrial|Branched-chain-amino-acid aminotransferase, cytosolic leu, ile, or val + alpha-ketoglutarate <=> branched-chain ketoacids + glutamate (human Reactome reaction) no branched_chain_amino_acid_catabolism Branched-chain amino acid (BCAA) catabolism — transamination and the BCKDH complex modules/branched_chain_amino_acid_catabolism.yaml R-HSA-70895 module_evidence "Step order and reactions follow the human Reactome ""Branched-chain amino acid catabolism"" pathway (R-HSA-70895), including the BCAT2 transamination (R-HSA-70724)." yes reactome/R-HSA-70895.md Branched-chain amino acid catabolism Homo sapiens carnitine_shuttle Carnitine shuttle (mitochondrial import of long-chain fatty acids) modules/carnitine_shuttle.yaml R-HSA-165026 activity_evidence slc22a5_step L-carnitine import across the plasma membrane (Na+-dependent) TRANSPORT_STEP slc22a5_activity SLC22A5/OCTN2: Na+-dependent carnitine transporter GO:0015226 carnitine transmembrane transporter activity UniProtKB:O76082 Organic cation/carnitine transporter 2 OCTN2 / SLC22A5 transports CAR from extracellular space to cytosol (human Reactome reaction) no carnitine_shuttle Carnitine shuttle (mitochondrial import of long-chain fatty acids) modules/carnitine_shuttle.yaml R-HSA-200406 activity_evidence cpt1_step long-chain acyl-CoA + L-carnitine to long-chain acylcarnitine + CoA REACTION cpt1a_activity CPT1A: carnitine palmitoyltransferase 1 (liver) GO:0004095 carnitine O-palmitoyltransferase activity UniProtKB:P50416 Carnitine O-palmitoyltransferase 1, liver isoform CPT1A transfers PALM to CAR (human Reactome reaction) no carnitine_shuttle Carnitine shuttle (mitochondrial import of long-chain fatty acids) modules/carnitine_shuttle.yaml R-HSA-200410 activity_evidence cpt2_step long-chain acylcarnitine + CoA to long-chain acyl-CoA + L-carnitine REACTION cpt2_activity CPT2: carnitine palmitoyltransferase 2 GO:0004095 carnitine O-palmitoyltransferase activity UniProtKB:P23786 Carnitine O-palmitoyltransferase 2, mitochondrial CPT2 converts acylcarnitine to acyl-CoA (human Reactome reaction) no carnitine_shuttle Carnitine shuttle (mitochondrial import of long-chain fatty acids) modules/carnitine_shuttle.yaml R-HSA-200424 activity_evidence slc25a20_step acylcarnitine (cytosolic) / carnitine (matrix) antiport TRANSPORT_STEP slc25a20_activity SLC25A20/CACT: carnitine-acylcarnitine translocase GO:0015227 O-acyl-L-carnitine transmembrane transporter activity UniProtKB:O43772 Mitochondrial carnitine/acylcarnitine carrier protein Exchange of acylcarnitine and carnitine across the inner mitochondrial membrane (human Reactome reaction) no carnitine_shuttle Carnitine shuttle (mitochondrial import of long-chain fatty acids) modules/carnitine_shuttle.yaml R-HSA-200425 module_evidence "Step order and reaction directions follow the human Reactome ""Carnitine shuttle"" pathway (R-HSA-200425): R-HSA-165026 (SLC22A5 uptake), R-HSA-200406 (CPT1A), R-HSA-200424 (SLC25A20 antiport) and R-HSA-200410 (CPT2)." yes reactome/R-HSA-200425.md Carnitine shuttle Homo sapiens cholesterol_synthesis_post_lanosterol Cholesterol biosynthesis II — lanosterol to cholesterol (post-lanosterol); SLOS, CDPX2, CHILD, lathosterolosis modules/cholesterol_synthesis_post_lanosterol.yaml R-HSA-191273 module_evidence Reactions follow the human Reactome cholesterol-biosynthesis pathway: R-HSA-194678 (CYP51A1), R-HSA-194641 (MSMO1), R-HSA-194642 (NSDHL), R-HSA-6807052 (EBP), R-HSA-195664 (SC5D) and R-HSA-196402 (DHCR7). yes reactome/R-HSA-191273.md Cholesterol biosynthesis Homo sapiens cholesterol_synthesis_post_lanosterol Cholesterol biosynthesis II — lanosterol to cholesterol (post-lanosterol); SLOS, CDPX2, CHILD, lathosterolosis modules/cholesterol_synthesis_post_lanosterol.yaml R-HSA-194641 activity_evidence msmo1_step 4,4-dimethyl/4-methyl sterol to 4-carboxy sterol (C4-methyl oxidation) REACTION msmo1_activity MSMO1: C4-methylsterol oxidase GO:0000254 C-4 methylsterol oxidase activity UniProtKB:Q15800 Methylsterol monooxygenase 1 4,4-dimethylcholesta-8(9),24-dien-3beta-ol is oxidized to 4-methyl... (human Reactome reaction) yes reactome/R-HSA-194641.md 4,4-dimethylcholesta-8(9),24-dien-3beta-ol is oxidized to 4-methyl,4-carboxycholesta-8(9),24-dien-3beta-ol Homo sapiens cholesterol_synthesis_post_lanosterol Cholesterol biosynthesis II — lanosterol to cholesterol (post-lanosterol); SLOS, CDPX2, CHILD, lathosterolosis modules/cholesterol_synthesis_post_lanosterol.yaml R-HSA-194642 activity_evidence nsdhl_step 4-carboxy sterol to 3-keto sterol + CO2 (then reduced to 3-beta-ol) REACTION nsdhl_activity NSDHL: sterol-4-carboxylate 3-dehydrogenase (decarboxylating) GO:0000252 3-beta-hydroxysteroid dehydrogenase [NAD(P)+]/C4-decarboxylase activity UniProtKB:Q15738 Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating 4-methyl,4-carboxycholesta-8(9),24-dien-3beta-ol is decarboxylated (human Reactome reaction) yes reactome/R-HSA-194642.md 4-methyl,4-carboxycholesta-8(9),24-dien-3beta-ol is decarboxylated and oxidized to form 4-methylcholesta-8(9),24-dien-3-one Homo sapiens cholesterol_synthesis_post_lanosterol Cholesterol biosynthesis II — lanosterol to cholesterol (post-lanosterol); SLOS, CDPX2, CHILD, lathosterolosis modules/cholesterol_synthesis_post_lanosterol.yaml R-HSA-194678 activity_evidence cyp51a1_step lanosterol to 14-demethyl-lanosterol (FF-MAS) REACTION cyp51a1_activity CYP51A1: sterol 14-alpha-demethylase GO:0008398 sterol 14-demethylase activity UniProtKB:Q16850 Lanosterol 14-alpha demethylase CYP51A1 demethylates LAN (human Reactome reaction) yes reactome/R-HSA-194678.md CYP51A1 demethylates LAN Homo sapiens cholesterol_synthesis_post_lanosterol Cholesterol biosynthesis II — lanosterol to cholesterol (post-lanosterol); SLOS, CDPX2, CHILD, lathosterolosis modules/cholesterol_synthesis_post_lanosterol.yaml R-HSA-195664 activity_evidence sc5d_step Delta(7)-sterol (lathosterol) to Delta(5,7)-sterol (7-dehydrocholesterol) REACTION sc5d_activity SC5D: lathosterol oxidase (sterol-C5-desaturase) GO:0050046 delta7-sterol 5(6)-desaturase activity UniProtKB:O75845 Lathosterol oxidase Cholesta-7,24-dien-3beta-ol is desaturated to form cholesta-5,7,24... (human Reactome reaction) yes reactome/R-HSA-195664.md Cholesta-7,24-dien-3beta-ol is desaturated to form cholesta-5,7,24-trien-3beta-ol Homo sapiens cholesterol_synthesis_post_lanosterol Cholesterol biosynthesis II — lanosterol to cholesterol (post-lanosterol); SLOS, CDPX2, CHILD, lathosterolosis modules/cholesterol_synthesis_post_lanosterol.yaml R-HSA-196402 activity_evidence dhcr7_step 7-dehydrocholesterol to cholesterol REACTION dhcr7_activity DHCR7: 7-dehydrocholesterol reductase GO:0047598 7-dehydrocholesterol reductase activity UniProtKB:Q9UBM7 7-dehydrocholesterol reductase Cholesta-5,7,24-trien-3beta-ol is reduced to desmosterol (human Reactome reaction) yes reactome/R-HSA-196402.md Cholesta-5,7,24-trien-3beta-ol is reduced to desmosterol Homo sapiens cholesterol_synthesis_post_lanosterol Cholesterol biosynthesis II — lanosterol to cholesterol (post-lanosterol); SLOS, CDPX2, CHILD, lathosterolosis modules/cholesterol_synthesis_post_lanosterol.yaml R-HSA-6807052 activity_evidence ebp_step Delta(8)-sterol to Delta(7)-sterol REACTION ebp_activity EBP: sterol Delta(8),Delta(7)-isomerase GO:0000247 C-8 sterol isomerase activity UniProtKB:Q15125 3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase EBP isomerizes ZYMSTNL to LTHSOL (human Reactome reaction) yes reactome/R-HSA-6807052.md EBP isomerizes ZYMSTNL to LTHSOL Homo sapiens cobalamin_absorption_transport Cobalamin (vitamin B12) absorption and transport; TCN1/CBLIF/CUBN/AMN/TCN2/CD320 modules/cobalamin_absorption_transport.yaml R-HSA-3000074 activity_evidence tcn2_step absorbed cobalamin bound by transcobalamin (TCN2) REACTION tcn2_activity TCN2: transcobalamin GO:0031419 cobalamin binding UniProtKB:P20062 Transcobalamin-2 TCN2 binds RCbl in the circulation (human Reactome reaction) yes reactome/R-HSA-3000074.md TCN2 binds RCbl in the circulation Homo sapiens cobalamin_absorption_transport Cobalamin (vitamin B12) absorption and transport; TCN1/CBLIF/CUBN/AMN/TCN2/CD320 modules/cobalamin_absorption_transport.yaml R-HSA-3000103 activity_evidence cubam_step IF-cobalamin internalised by the cubam receptor (CUBN/AMN) PROTEIN_COMPLEX amn_activity AMN: amnionless (cubam membrane-anchor/endocytic subunit) GO:0038024 cargo receptor activity UniProtKB:Q9BXJ7 Protein amnionless CUBN:AMN binds CBLIF:RCbl (human Reactome reaction) yes reactome/R-HSA-3000103.md CUBN:AMN binds CBLIF:RCbl Homo sapiens cobalamin_absorption_transport Cobalamin (vitamin B12) absorption and transport; TCN1/CBLIF/CUBN/AMN/TCN2/CD320 modules/cobalamin_absorption_transport.yaml R-HSA-3000103 activity_evidence cubam_step IF-cobalamin internalised by the cubam receptor (CUBN/AMN) PROTEIN_COMPLEX cubn_activity CUBN: cubilin (cubam ligand-binding subunit) GO:0038024 cargo receptor activity UniProtKB:O60494 Cubilin CUBN:AMN binds CBLIF:RCbl (human Reactome reaction) yes reactome/R-HSA-3000103.md CUBN:AMN binds CBLIF:RCbl Homo sapiens cobalamin_absorption_transport Cobalamin (vitamin B12) absorption and transport; TCN1/CBLIF/CUBN/AMN/TCN2/CD320 modules/cobalamin_absorption_transport.yaml R-HSA-3000112 activity_evidence cd320_step TC-cobalamin internalised by CD320 (TCblR) REACTION cd320_activity CD320: transcobalamin receptor (TCblR) GO:0038024 cargo receptor activity UniProtKB:Q9NPF0 CD320 antigen (transcobalamin receptor) CD320-mediated TCN2:RCbl uptake and delivery to lysosome (human Reactome reaction) yes reactome/R-HSA-3000112.md CD320-mediated TCN2:RCbl uptake and delivery to lysosome Homo sapiens cobalamin_absorption_transport Cobalamin (vitamin B12) absorption and transport; TCN1/CBLIF/CUBN/AMN/TCN2/CD320 modules/cobalamin_absorption_transport.yaml R-HSA-3000120 activity_evidence cblif_step cobalamin bound by intrinsic factor (CBLIF) REACTION cblif_activity CBLIF: gastric intrinsic factor GO:0031419 cobalamin binding UniProtKB:P27352 Gastric intrinsic factor CBLIF binds RCbl (human Reactome reaction) yes reactome/R-HSA-3000120.md CBLIF binds RCbl Homo sapiens cobalamin_absorption_transport Cobalamin (vitamin B12) absorption and transport; TCN1/CBLIF/CUBN/AMN/TCN2/CD320 modules/cobalamin_absorption_transport.yaml R-HSA-3000122 activity_evidence cd320_step TC-cobalamin internalised by CD320 (TCblR) REACTION cd320_activity CD320: transcobalamin receptor (TCblR) GO:0038024 cargo receptor activity UniProtKB:Q9NPF0 CD320 antigen (transcobalamin receptor) CD320 binds extracellular TCN2:RCbl (human Reactome reaction) yes reactome/R-HSA-3000122.md CD320 binds extracellular TCN2:RCbl Homo sapiens cobalamin_absorption_transport Cobalamin (vitamin B12) absorption and transport; TCN1/CBLIF/CUBN/AMN/TCN2/CD320 modules/cobalamin_absorption_transport.yaml R-HSA-3000137 module_evidence "The ileal intrinsic-factor-cobalamin uptake step follows the human Reactome ""CUBN:AMN-mediated CBLIF:RCbl uptake"" reaction; the plasma-transport/CD320 steps follow R-HSA-3000074/3000112/3000122." yes reactome/R-HSA-3000137.md CUBN:AMN-mediated CBLIF:RCbl uptake and delivery to lysosome Homo sapiens cobalamin_absorption_transport Cobalamin (vitamin B12) absorption and transport; TCN1/CBLIF/CUBN/AMN/TCN2/CD320 modules/cobalamin_absorption_transport.yaml R-HSA-3000137 activity_evidence cubam_step IF-cobalamin internalised by the cubam receptor (CUBN/AMN) PROTEIN_COMPLEX cubn_activity CUBN: cubilin (cubam ligand-binding subunit) GO:0038024 cargo receptor activity UniProtKB:O60494 Cubilin CUBN:AMN-mediated CBLIF:RCbl uptake and delivery to lysosome (human Reactome reaction) yes reactome/R-HSA-3000137.md CUBN:AMN-mediated CBLIF:RCbl uptake and delivery to lysosome Homo sapiens cobalamin_absorption_transport Cobalamin (vitamin B12) absorption and transport; TCN1/CBLIF/CUBN/AMN/TCN2/CD320 modules/cobalamin_absorption_transport.yaml R-HSA-3132759 activity_evidence tcn1_step cobalamin bound by haptocorrin (TCN1) REACTION tcn1_activity TCN1: haptocorrin (transcobalamin I) GO:0031419 cobalamin binding UniProtKB:P20061 Transcobalamin-1 (haptocorrin) TCN1 binds RCbl (human Reactome reaction) yes reactome/R-HSA-3132759.md TCN1 binds RCbl Homo sapiens cobalamin_intracellular_processing Cobalamin (B12) intracellular processing and trafficking; ABCD4/LMBRD1/MMACHC/MMADHC modules/cobalamin_intracellular_processing.yaml R-HSA-3149494 activity_evidence mmachc_step cobalamin decyanation/dealkylation to cob(II)alamin (MMACHC) REACTION mmachc_activity MMACHC: cyanocobalamin reductase / cobalamin dealkylase (cblC) GO:0033787 cyanocobalamin reductase (cyanide-eliminating) (NADP+) activity UniProtKB:Q9Y4U1 Cyanocobalamin reductase / alkylcobalamin dealkylase MMACHC:cob(II)alamin binds MMADHC (human Reactome reaction) yes reactome/R-HSA-3149494.md MMACHC:cob(II)alamin binds MMADHC Homo sapiens cobalamin_intracellular_processing Cobalamin (B12) intracellular processing and trafficking; ABCD4/LMBRD1/MMACHC/MMADHC modules/cobalamin_intracellular_processing.yaml R-HSA-3149563 activity_evidence mmadhc_step cob(II)alamin routed to the AdoCbl or MeCbl branch (MMADHC) REACTION mmadhc_activity MMADHC: cobalamin branch-point trafficking protein (cblD) GO:0140104 molecular carrier activity UniProtKB:Q9H3L0 Methylmalonic aciduria and homocystinuria type D protein MMADHC targets transport of cytosolic cob(II)alamin to mitochondrion (human Reactome reaction) yes reactome/R-HSA-3149563.md MMADHC targets transport of cytosolic cob(II)alamin to mitochondria Homo sapiens cobalamin_intracellular_processing Cobalamin (B12) intracellular processing and trafficking; ABCD4/LMBRD1/MMACHC/MMADHC modules/cobalamin_intracellular_processing.yaml R-HSA-5223313 node_evidence lysosomal_export_step cobalamin export from lysosomal lumen to cytosol (ABCD4:LMBRD1) PROTEIN_COMPLEX ABCD4:LMBRD1 transports RCbl from lysosomal lumen to cytosol (human Reactome reaction) yes reactome/R-HSA-5223313.md ABCD4:LMBRD1 transports RCbl from lysosomal lumen to cytosol (gut mucosal cells) Homo sapiens cobalamin_intracellular_processing Cobalamin (B12) intracellular processing and trafficking; ABCD4/LMBRD1/MMACHC/MMADHC modules/cobalamin_intracellular_processing.yaml R-HSA-5223313 activity_evidence lysosomal_export_step cobalamin export from lysosomal lumen to cytosol (ABCD4:LMBRD1) PROTEIN_COMPLEX abcd4_activity ABCD4: lysosomal ABC cobalamin transporter (cblJ) GO:0015420 ABC-type vitamin B12 transporter activity UniProtKB:O14678 ATP-binding cassette sub-family D member 4 ABCD4:LMBRD1 transports RCbl from lysosomal lumen to cytosol (human Reactome reaction) yes reactome/R-HSA-5223313.md ABCD4:LMBRD1 transports RCbl from lysosomal lumen to cytosol (gut mucosal cells) Homo sapiens cobalamin_intracellular_processing Cobalamin (B12) intracellular processing and trafficking; ABCD4/LMBRD1/MMACHC/MMADHC modules/cobalamin_intracellular_processing.yaml R-HSA-9759218 module_evidence "Step order and intermediates follow the human Reactome ""Cobalamin (Cbl) metabolism"" pathway (reactions R-HSA-5223313 lysosomal export, R-HSA-3149494/3149563 MMACHC/MMADHC processing)." yes reactome/R-HSA-9759218.md Cobalamin (Cbl) metabolism Homo sapiens complex_i_assembly_factors Mitochondrial Complex I (NADH:ubiquinone oxidoreductase) assembly factors; NDUFAF1-8/NUBPL/FOXRED1/TIMMDC1 modules/complex_i_assembly_factors.yaml R-HSA-6799198 module_evidence "The ordered, factor-dependent assembly follows the human Reactome ""Complex I biogenesis"" pathway (R-HSA-6799198)." yes reactome/R-HSA-6799198.md Complex I biogenesis Homo sapiens complex_iv_assembly_factors Mitochondrial Complex IV (cytochrome c oxidase) assembly factors; TACO1/COA3/COX11/COA6/COX16/COA5/COX18/COA7/PET100/PET117 modules/complex_iv_assembly_factors.yaml R-HSA-9864848 module_evidence "The MT-CO1/MT-CO2 metallation and subunit-incorporation steps follow the human Reactome ""Complex IV assembly"" pathway (R-HSA-9865449 CuB, R-HSA-9865630 CuA, R-HSA-9902096 COX18)." yes reactome/R-HSA-9864848.md Complex IV assembly Homo sapiens complex_iv_assembly_factors Mitochondrial Complex IV (cytochrome c oxidase) assembly factors; TACO1/COA3/COX11/COA6/COX16/COA5/COX18/COA7/PET100/PET117 modules/complex_iv_assembly_factors.yaml R-HSA-9865449 activity_evidence cub_metallation copper insertion into the MT-CO1 CuB site REACTION cox11_activity COX11: CuB copper chaperone GO:0016531 copper chaperone activity UniProtKB:Q9Y6N1 Cytochrome c oxidase assembly protein COX11 Metallochaperone inserts Cu2+ into MT-CO1 (human Reactome reaction) yes reactome/R-HSA-9865449.md Metallochaperone inserts Cu2+ into MT-CO1 Homo sapiens complex_iv_assembly_factors Mitochondrial Complex IV (cytochrome c oxidase) assembly factors; TACO1/COA3/COX11/COA6/COX16/COA5/COX18/COA7/PET100/PET117 modules/complex_iv_assembly_factors.yaml R-HSA-9865630 activity_evidence cua_metallation MT-CO2 CuA site copper delivery and disulfide relay REACTION coa6_activity COA6: CuA copper-relay disulfide reductase GO:0015035 protein-disulfide reductase activity UniProtKB:Q5JTJ3 Cytochrome c oxidase assembly factor 6 homolog Metallochaperone inserts 2Cu2+ into MT-CO2 (human Reactome reaction) yes reactome/R-HSA-9865630.md Metallochaperone inserts 2Cu2+ into MT-CO2 Homo sapiens complex_iv_assembly_factors Mitochondrial Complex IV (cytochrome c oxidase) assembly factors; TACO1/COA3/COX11/COA6/COX16/COA5/COX18/COA7/PET100/PET117 modules/complex_iv_assembly_factors.yaml R-HSA-9902096 activity_evidence mtco2_insertion MT-CO2 C-terminal membrane insertion REACTION cox18_activity COX18: MT-CO2 membrane insertase GO:0032977 membrane insertase activity UniProtKB:Q8N8Q8 Mitochondrial inner membrane protein COX18 COX18 inserts nascent MT-CO2 in COX20:TMEM77 (human Reactome reaction) yes reactome/R-HSA-9902096.md COX18 inserts nascent MT-CO2 in COX20:TMEM77 Homo sapiens cortisol_cortisone_shuttle Cortisol-cortisone shuttle — pre-receptor glucocorticoid interconversion; HSD11B1/HSD11B2 modules/cortisol_cortisone_shuttle.yaml R-HSA-194023 module_evidence The cortisol->cortisone oxidation is the human Reactome reaction R-HSA-194023; HSD11B1 also runs the reverse (cortisone->cortisol) reduction in vivo. yes reactome/R-HSA-194023.md HSD11B2,HSD11B1 dimer oxidise CORT to COR Homo sapiens cortisol_cortisone_shuttle Cortisol-cortisone shuttle — pre-receptor glucocorticoid interconversion; HSD11B1/HSD11B2 modules/cortisol_cortisone_shuttle.yaml R-HSA-194023 activity_evidence hsd11b1_step cortisone to cortisol (NADPH-dependent reductase) REACTION hsd11b1_activity HSD11B1: 11beta-hydroxysteroid dehydrogenase type 1 GO:0070524 11-beta-hydroxysteroid dehydrogenase (NADP+) activity UniProtKB:P28845 11-beta-hydroxysteroid dehydrogenase 1 HSD11B2,HSD11B1 dimer oxidise CORT to COR (human Reactome reaction); HSD11B1 runs the reverse reductase direction in vivo yes reactome/R-HSA-194023.md HSD11B2,HSD11B1 dimer oxidise CORT to COR Homo sapiens cortisol_cortisone_shuttle Cortisol-cortisone shuttle — pre-receptor glucocorticoid interconversion; HSD11B1/HSD11B2 modules/cortisol_cortisone_shuttle.yaml R-HSA-194023 activity_evidence hsd11b2_step cortisol to cortisone (NAD+-dependent dehydrogenase) REACTION hsd11b2_activity HSD11B2: 11beta-hydroxysteroid dehydrogenase type 2 GO:0070523 11-beta-hydroxysteroid dehydrogenase (NAD+) activity UniProtKB:P80365 11-beta-hydroxysteroid dehydrogenase type 2 HSD11B2,HSD11B1 dimer oxidise CORT to COR (human Reactome reaction) yes reactome/R-HSA-194023.md HSD11B2,HSD11B1 dimer oxidise CORT to COR Homo sapiens creatine_biosynthesis Creatine biosynthesis (vertebrate, two-step AGAT to GAMT) modules/creatine_biosynthesis.yaml R-HSA-71275 activity_evidence agat_step L-arginine + glycine to guanidinoacetate + L-ornithine REACTION gatm_activity GATM/AGAT: glycine amidinotransferase GO:0015068 glycine amidinotransferase activity UniProtKB:P50440 Glycine amidinotransferase, mitochondrial arginine + glycine => ornithine + guanidoacetate (human Reactome reaction) no creatine_biosynthesis Creatine biosynthesis (vertebrate, two-step AGAT to GAMT) modules/creatine_biosynthesis.yaml R-HSA-71286 activity_evidence gamt_step guanidinoacetate + SAM to creatine + SAH REACTION gamt_activity GAMT: guanidinoacetate N-methyltransferase GO:0030731 guanidinoacetate N-methyltransferase activity UniProtKB:Q14353 Guanidinoacetate N-methyltransferase guanidinoacetate + S-adenosylmethionine => creatine + S-adenosylhomocysteine (human Reactome reaction) yes reactome/R-HSA-71286.md guanidinoacetate + S-adenosylmethionine => creatine + S-adenosylhomocysteine Homo sapiens creatine_phosphocreatine_system Creatine-phosphocreatine system (human) modules/creatine_phosphocreatine_system.yaml R-HSA-200396 module_evidence Reactome reaction grounding the SLC6A8 transport part of the system (now grounded to the reviewed human gene SLC6A8). yes reactome/R-HSA-200396.md Creatine transport across the plasma membrane Homo sapiens creatine_phosphocreatine_system Creatine-phosphocreatine system (human) modules/creatine_phosphocreatine_system.yaml R-HSA-200396 activity_evidence transport_part Creatine transport (SLC6A8) TRANSPORT_STEP slc6a8_activity SLC6A8: Na+/Cl--dependent creatine transporter GO:0005309 creatine:sodium symporter activity UniProtKB:P48029 Sodium- and chloride-dependent creatine transporter 1 Creatine transport across the plasma membrane (Reactome reaction) yes reactome/R-HSA-200396.md Creatine transport across the plasma membrane Homo sapiens creatine_phosphocreatine_system Creatine-phosphocreatine system (human) modules/creatine_phosphocreatine_system.yaml R-HSA-71287 module_evidence Reactome reaction for the spontaneous, non-enzymatic creatinine-disposal (catabolic) exit of the system, recorded at the concept level (GO:0046449). no creatine_phosphocreatine_system Creatine-phosphocreatine system (human) modules/creatine_phosphocreatine_system.yaml R-HSA-71288 module_evidence "Reactome groups creatine biosynthesis and the creatine kinase reactions under a single ""Creatine metabolism"" event; this system node mirrors that scope while keeping the GO branches distinct." yes reactome/R-HSA-71288.md Creatine metabolism Homo sapiens de_novo_pyrimidine_synthesis De novo pyrimidine synthesis (glutamine -> UMP); orotic aciduria, Miller syndrome, CAD-DEE modules/de_novo_pyrimidine_synthesis.yaml R-HSA-500753 module_evidence Step order and reaction stoichiometries follow the human Reactome pyrimidine biosynthesis reactions R-HSA-73577/73573/73571 (CAD), R-HSA-73569 (DHODH) and R-HSA-73567/73564 (UMPS). yes reactome/R-HSA-500753.md Pyrimidine biosynthesis Homo sapiens de_novo_pyrimidine_synthesis De novo pyrimidine synthesis (glutamine -> UMP); orotic aciduria, Miller syndrome, CAD-DEE modules/de_novo_pyrimidine_synthesis.yaml R-HSA-73564 activity_evidence umps_step orotate + PRPP -> OMP -> UMP + CO2 REACTION umps_activity UMPS: bifunctional OPRT / OMP decarboxylase GO:0004588 orotate phosphoribosyltransferase activity UniProtKB:P11172 Uridine 5'-monophosphate synthase UMPS dimer decarboxylates OMP to UMP (human Reactome reaction) yes reactome/R-HSA-73564.md UMPS dimer decarboxylates OMP to UMP Homo sapiens de_novo_pyrimidine_synthesis De novo pyrimidine synthesis (glutamine -> UMP); orotic aciduria, Miller syndrome, CAD-DEE modules/de_novo_pyrimidine_synthesis.yaml R-HSA-73567 activity_evidence umps_step orotate + PRPP -> OMP -> UMP + CO2 REACTION umps_activity UMPS: bifunctional OPRT / OMP decarboxylase GO:0004588 orotate phosphoribosyltransferase activity UniProtKB:P11172 Uridine 5'-monophosphate synthase UMPS dimer transfers phosphoribosyl group to ORO to form OMP (human Reactome reaction) yes reactome/R-HSA-73567.md UMPS dimer transfers phosphoribosyl group to ORO to form OMP Homo sapiens de_novo_pyrimidine_synthesis De novo pyrimidine synthesis (glutamine -> UMP); orotic aciduria, Miller syndrome, CAD-DEE modules/de_novo_pyrimidine_synthesis.yaml R-HSA-73569 activity_evidence dhodh_step (S)-dihydroorotate + ubiquinone to orotate + ubiquinol REACTION dhodh_activity DHODH: dihydroorotate dehydrogenase (quinone) GO:0106430 dihydroorotate dehydrogenase (quinone) activity UniProtKB:Q02127 Dihydroorotate dehydrogenase (quinone), mitochondrial DHODH:FMN oxidises (S)-DHO to orotate (human Reactome reaction) yes reactome/R-HSA-73569.md DHODH:FMN oxidises (S)-DHO to orotate Homo sapiens de_novo_pyrimidine_synthesis De novo pyrimidine synthesis (glutamine -> UMP); orotic aciduria, Miller syndrome, CAD-DEE modules/de_novo_pyrimidine_synthesis.yaml R-HSA-73571 activity_evidence cad_step L-glutamine + HCO3- + ATP -> ... -> (S)-dihydroorotate REACTION cad_activity CAD: CPS II / aspartate transcarbamylase / dihydroorotase GO:0004088 carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity UniProtKB:P27708 CAD protein (glutamine-dependent carbamoyl-phosphate synthase / aspartate carbamoyltransferase / dihydroorotase) CAD hexamer dehydrates N-carb-L-Asp to (S)-DHO (human Reactome reaction) yes reactome/R-HSA-73571.md CAD hexamer dehydrates N-carb-L-Asp to (S)-DHO Homo sapiens de_novo_pyrimidine_synthesis De novo pyrimidine synthesis (glutamine -> UMP); orotic aciduria, Miller syndrome, CAD-DEE modules/de_novo_pyrimidine_synthesis.yaml R-HSA-73573 activity_evidence cad_step L-glutamine + HCO3- + ATP -> ... -> (S)-dihydroorotate REACTION cad_activity CAD: CPS II / aspartate transcarbamylase / dihydroorotase GO:0004088 carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity UniProtKB:P27708 CAD protein (glutamine-dependent carbamoyl-phosphate synthase / aspartate carbamoyltransferase / dihydroorotase) CAD hexamer transforms CAP to N-carb-L-Asp (human Reactome reaction) yes reactome/R-HSA-73573.md CAD hexamer transforms CAP to N-carb-L-Asp Homo sapiens de_novo_pyrimidine_synthesis De novo pyrimidine synthesis (glutamine -> UMP); orotic aciduria, Miller syndrome, CAD-DEE modules/de_novo_pyrimidine_synthesis.yaml R-HSA-73577 activity_evidence cad_step L-glutamine + HCO3- + ATP -> ... -> (S)-dihydroorotate REACTION cad_activity CAD: CPS II / aspartate transcarbamylase / dihydroorotase GO:0004088 carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity UniProtKB:P27708 CAD protein (glutamine-dependent carbamoyl-phosphate synthase / aspartate carbamoyltransferase / dihydroorotase) CAD hexamer transforms L-Gln to CAP (human Reactome reaction) yes reactome/R-HSA-73577.md CAD hexamer transforms L-Gln to CAP Homo sapiens dolichol_phosphate_sugar_donor_supply Dolichol phosphate and lipid-linked sugar-donor supply for glycosylation; SRD5A3/DOLK/DPM1/DPM2/DPM3/ALG5/MPDU1 modules/dolichol_phosphate_sugar_donor_supply.yaml R-HSA-162699 module_evidence "The Dol-P-Man branch (DPM1/DPM2/DPM3 complex) follows the human Reactome ""Synthesis of dolichyl-phosphate mannose"" sub-pathway (reaction R-HSA-162721)." yes reactome/R-HSA-162699.md Synthesis of dolichyl-phosphate mannose Homo sapiens dolichol_phosphate_sugar_donor_supply Dolichol phosphate and lipid-linked sugar-donor supply for glycosylation; SRD5A3/DOLK/DPM1/DPM2/DPM3/ALG5/MPDU1 modules/dolichol_phosphate_sugar_donor_supply.yaml R-HSA-162699 activity_evidence dpm_complex_step GDP-mannose + Dol-P to dolichyl-phosphate-mannose (Dol-P-Man) PROTEIN_COMPLEX dpm2_activity DPM2: DPM synthase regulatory subunit GO:0008047 enzyme activator activity UniProtKB:O94777 Dolichol-phosphate mannosyltransferase subunit 2 Synthesis of dolichyl-phosphate mannose (human Reactome sub-pathway) yes reactome/R-HSA-162699.md Synthesis of dolichyl-phosphate mannose Homo sapiens dolichol_phosphate_sugar_donor_supply Dolichol phosphate and lipid-linked sugar-donor supply for glycosylation; SRD5A3/DOLK/DPM1/DPM2/DPM3/ALG5/MPDU1 modules/dolichol_phosphate_sugar_donor_supply.yaml R-HSA-162699 activity_evidence dpm_complex_step GDP-mannose + Dol-P to dolichyl-phosphate-mannose (Dol-P-Man) PROTEIN_COMPLEX dpm3_activity DPM3: DPM synthase membrane anchor GO:0043495 protein-membrane adaptor activity UniProtKB:Q9P2X0 Dolichol-phosphate mannosyltransferase subunit 3 Synthesis of dolichyl-phosphate mannose (human Reactome sub-pathway) yes reactome/R-HSA-162699.md Synthesis of dolichyl-phosphate mannose Homo sapiens dolichol_phosphate_sugar_donor_supply Dolichol phosphate and lipid-linked sugar-donor supply for glycosylation; SRD5A3/DOLK/DPM1/DPM2/DPM3/ALG5/MPDU1 modules/dolichol_phosphate_sugar_donor_supply.yaml R-HSA-162721 activity_evidence dpm_complex_step GDP-mannose + Dol-P to dolichyl-phosphate-mannose (Dol-P-Man) PROTEIN_COMPLEX dpm1_activity DPM1: Dol-P-Man synthase catalytic subunit GO:0004582 dolichyl-phosphate beta-D-mannosyltransferase activity UniProtKB:O60762 Dolichol-phosphate mannosyltransferase subunit 1 dolichyl phosphate + GDP-alpha-D-mannose -> dolichyl phosphate-mannose (human Reactome reaction) yes reactome/R-HSA-162721.md dolichyl phosphate + GDP-alpha-D-mannose -> dolichyl phosphate D-mannose Homo sapiens dolichol_phosphate_sugar_donor_supply Dolichol phosphate and lipid-linked sugar-donor supply for glycosylation; SRD5A3/DOLK/DPM1/DPM2/DPM3/ALG5/MPDU1 modules/dolichol_phosphate_sugar_donor_supply.yaml R-HSA-446195 activity_evidence dolk_step dolichol to dolichyl phosphate (Dol-P) REACTION dolk_activity DOLK: dolichol kinase GO:0004168 dolichol kinase activity UniProtKB:Q9UPQ8 Dolichol kinase DOLK phosphorylates DCHOL to DOLP (human Reactome reaction) yes reactome/R-HSA-446195.md DOLK phosphorylates DCHOL to DOLP Homo sapiens dolichol_phosphate_sugar_donor_supply Dolichol phosphate and lipid-linked sugar-donor supply for glycosylation; SRD5A3/DOLK/DPM1/DPM2/DPM3/ALG5/MPDU1 modules/dolichol_phosphate_sugar_donor_supply.yaml R-HSA-446199 module_evidence "The dolichol -> Dol-P segment (SRD5A3 polyprenol reduction, DOLK phosphorylation) follows the human Reactome ""Synthesis of dolichyl-phosphate"" sub-pathway." yes reactome/R-HSA-446199.md Synthesis of dolichyl-phosphate Homo sapiens dolichol_phosphate_sugar_donor_supply Dolichol phosphate and lipid-linked sugar-donor supply for glycosylation; SRD5A3/DOLK/DPM1/DPM2/DPM3/ALG5/MPDU1 modules/dolichol_phosphate_sugar_donor_supply.yaml R-HSA-446199 activity_evidence srd5a3_step polyprenol to dolichol REACTION srd5a3_activity SRD5A3: polyprenol reductase GO:0160198 polyprenal reductase activity UniProtKB:Q9H8P0 Polyprenol reductase Synthesis of dolichyl-phosphate (human Reactome sub-pathway; includes polyprenol reduction to dolichol) yes reactome/R-HSA-446199.md Synthesis of dolichyl-phosphate Homo sapiens dolichol_phosphate_sugar_donor_supply Dolichol phosphate and lipid-linked sugar-donor supply for glycosylation; SRD5A3/DOLK/DPM1/DPM2/DPM3/ALG5/MPDU1 modules/dolichol_phosphate_sugar_donor_supply.yaml R-HSA-480985 activity_evidence alg5_step UDP-glucose + Dol-P to dolichyl-phosphate-glucose (Dol-P-Glc) REACTION alg5_activity ALG5: dolichyl-phosphate beta-glucosyltransferase GO:0004581 dolichyl-phosphate beta-glucosyltransferase activity UniProtKB:Q9Y673 Dolichyl-phosphate beta-glucosyltransferase Synthesis of dolichyl-phosphate-glucose (human Reactome reaction) yes reactome/R-HSA-480985.md Synthesis of dolichyl-phosphate-glucose Homo sapiens electron_transfer_flavoprotein_system Electron-transfer flavoprotein (ETF) system — electron sink for mitochondrial FAD dehydrogenases modules/electron_transfer_flavoprotein_system.yaml R-HSA-169260 activity_evidence etf_reduction_step acyl-CoA dehydrogenases reduce the ETF (ETFA/ETFB) flavoprotein PROTEIN_COMPLEX etfa_activity ETFA: electron transfer flavoprotein alpha (FAD-bearing) GO:0009055 electron transfer activity UniProtKB:P13804 Electron transfer flavoprotein subunit alpha, mitochondrial Reducing equivalents from beta-oxidation of fatty acids transfer to ETF (human Reactome reaction) no electron_transfer_flavoprotein_system Electron-transfer flavoprotein (ETF) system — electron sink for mitochondrial FAD dehydrogenases modules/electron_transfer_flavoprotein_system.yaml R-HSA-169260 activity_evidence etf_reduction_step acyl-CoA dehydrogenases reduce the ETF (ETFA/ETFB) flavoprotein PROTEIN_COMPLEX etfb_activity ETFB: electron transfer flavoprotein beta (dehydrogenase docking) GO:0009055 electron transfer activity UniProtKB:P38117 Electron transfer flavoprotein subunit beta Reducing equivalents from beta-oxidation of fatty acids transfer to ETF (human Reactome reaction) no electron_transfer_flavoprotein_system Electron-transfer flavoprotein (ETF) system — electron sink for mitochondrial FAD dehydrogenases modules/electron_transfer_flavoprotein_system.yaml R-HSA-169270 module_evidence The relay follows the human Reactome reactions R-HSA-169260 (acyl-CoA dehydrogenases reduce ETF) and R-HSA-169270 (ETFDH reoxidises ETF and reduces ubiquinone), feeding respiratory electron transport (R-HSA-611105). no electron_transfer_flavoprotein_system Electron-transfer flavoprotein (ETF) system — electron sink for mitochondrial FAD dehydrogenases modules/electron_transfer_flavoprotein_system.yaml R-HSA-169270 activity_evidence etfdh_step reduced ETF + ubiquinone to oxidised ETF + ubiquinol REACTION etfdh_activity ETFDH/ETF-QO: electron transfer flavoprotein-ubiquinone oxidoreductase GO:0004174 electron-transferring-flavoprotein dehydrogenase activity UniProtKB:Q16134 Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial ETFDH oxidises ETF (reduced) to ETF, reduces CoQ to CoQH2 (human Reactome reaction) no fructolysis Fructolysis (hepatic dietary fructose catabolism; hereditary fructose intolerance) modules/fructolysis.yaml R-HSA-70333 activity_evidence khk_step D-fructose + ATP to D-fructose-1-phosphate + ADP REACTION khk_activity KHK: ketohexokinase (fructokinase) GO:0004454 ketohexokinase activity UniProtKB:P50053 Ketohexokinase KHK dimer phosphorylates Fru to Fru 1-P (human Reactome reaction) no fructolysis Fructolysis (hepatic dietary fructose catabolism; hereditary fructose intolerance) modules/fructolysis.yaml R-HSA-70342 activity_evidence aldob_step D-fructose-1-phosphate to DHAP + D-glyceraldehyde REACTION aldob_activity ALDOB: fructose-bisphosphate aldolase B GO:0061609 fructose-1-phosphate aldolase activity UniProtKB:P05062 Fructose-bisphosphate aldolase B ALDOB tetramer cleaves Fru-1-P to GA and DHAP (human Reactome reaction) yes reactome/R-HSA-70342.md ALDOB tetramer cleaves Fru-1-P to GA and DHAP Homo sapiens fructolysis Fructolysis (hepatic dietary fructose catabolism; hereditary fructose intolerance) modules/fructolysis.yaml R-HSA-70349 activity_evidence tkfc_step D-glyceraldehyde + ATP to D-glyceraldehyde-3-phosphate + ADP REACTION tkfc_activity TKFC: triokinase GO:0050354 triokinase activity UniProtKB:Q3LXA3 Triokinase/FMN cyclase DAK dimer phosphorylates D-glyceraldehyde to form D-glyceraldehyde 3-phosphate (human Reactome reaction) no fructolysis Fructolysis (hepatic dietary fructose catabolism; hereditary fructose intolerance) modules/fructolysis.yaml R-HSA-70350 module_evidence "Step order and reaction stoichiometries follow the human Reactome ""Fructose catabolism"" reactions R-HSA-70333 (KHK), R-HSA-70342 (ALDOB) and R-HSA-70349 (TKFC)." yes reactome/R-HSA-70350.md Fructose catabolism Homo sapiens gaba_shunt Mammalian GABA shunt (glutamate to GABA to succinate) modules/gaba_shunt.yaml R-HSA-888548 activity_evidence aldh5a1_step succinate semialdehyde + NAD+ to succinate + NADH REACTION aldh5a1_activity ALDH5A1: succinate-semialdehyde dehydrogenase (SSADH) GO:0004777 succinate-semialdehyde dehydrogenase (NAD+) activity UniProtKB:P51649 Succinate-semialdehyde dehydrogenase, mitochondrial ALDH5A1 dehydrogenates SUCCSA to SUCCA (human Reactome reaction) yes reactome/R-HSA-888548.md ALDH5A1 dehydrogenates SUCCSA to SUCCA Homo sapiens gaba_shunt Mammalian GABA shunt (glutamate to GABA to succinate) modules/gaba_shunt.yaml R-HSA-888572 module_evidence Reactions follow the human Reactome GABA-metabolism reactions R-HSA-888572 (GAD1), R-HSA-916855 (ABAT) and R-HSA-888548 (ALDH5A1). yes reactome/R-HSA-888572.md PXLP-K405-GAD1 decarboxylates L-Glu to form GABA Homo sapiens gaba_shunt Mammalian GABA shunt (glutamate to GABA to succinate) modules/gaba_shunt.yaml R-HSA-888572 activity_evidence gad_step L-glutamate to GABA + CO2 REACTION gad_activity GAD1/GAD2: glutamate decarboxylase GO:0004351 glutamate decarboxylase activity UniProtKB:Q05329|UniProtKB:Q99259 Glutamate decarboxylase 2|Glutamate decarboxylase 1 PXLP-K405-GAD1 decarboxylates L-Glu to form GABA (human Reactome reaction) yes reactome/R-HSA-888572.md PXLP-K405-GAD1 decarboxylates L-Glu to form GABA Homo sapiens gaba_shunt Mammalian GABA shunt (glutamate to GABA to succinate) modules/gaba_shunt.yaml R-HSA-916855 activity_evidence abat_step GABA + 2-oxoglutarate to succinate semialdehyde + L-glutamate REACTION abat_activity ABAT: 4-aminobutyrate aminotransferase (GABA-T) GO:0034386 4-aminobutyrate:2-oxoglutarate transaminase activity UniProtKB:P80404 4-aminobutyrate aminotransferase, mitochondrial PXLP-K357-ABAT dimer:2Fe-2S transforms GABA to SUCCSA (human Reactome reaction) yes reactome/R-HSA-916855.md PXLP-K357-ABAT dimer:2Fe-2S transforms GABA to SUCCSA Homo sapiens galactose_leloir_pathway Galactose catabolism (Leloir pathway) modules/galactose_leloir_pathway.yaml R-HSA-70355 activity_evidence galk1_step alpha-D-galactose + ATP to alpha-D-galactose 1-phosphate + ADP REACTION galk1_activity GALK1: galactokinase GO:0004335 galactokinase activity UniProtKB:P0A6T3|UniProtKB:P51570 Galactokinase|Galactokinase GALK1 phosphorylates Gal to Gal1P (human Reactome reaction) no galactose_leloir_pathway Galactose catabolism (Leloir pathway) modules/galactose_leloir_pathway.yaml R-HSA-70361 activity_evidence galt_step alpha-D-galactose 1-phosphate + UDP-glucose to glucose-1-phosphate + UDP-galactose REACTION galt_activity GALT: galactose-1-phosphate uridylyltransferase GO:0008108 UDP-glucose:hexose-1-phosphate uridylyltransferase activity UniProtKB:P07902|UniProtKB:P09148 Galactose-1-phosphate uridylyltransferase|Galactose-1-phosphate uridylyltransferase GALT transfers UMP from UDP-Glc to Gal1P to form UDP-Gal (human Reactome reaction) no galactose_leloir_pathway Galactose catabolism (Leloir pathway) modules/galactose_leloir_pathway.yaml R-HSA-70369 activity_evidence gale_step UDP-galactose to UDP-glucose (reversible) REACTION gale_activity GALE: UDP-galactose-4-epimerase GO:0003978 UDP-glucose 4-epimerase activity UniProtKB:P09147|UniProtKB:Q14376|UniProtKB:Q88I72 UDP-glucose 4-epimerase|UDP-glucose 4-epimerase|UDP-glucose 4-epimerase GALE:NAD+ dimer reversibly epimerises UDP-Gal to UDP-Glc (human Reactome reaction) no galactose_leloir_pathway Galactose catabolism (Leloir pathway) modules/galactose_leloir_pathway.yaml R-HSA-70370 module_evidence "Step order and reaction stoichiometries follow the human Reactome ""Galactose catabolism"" pathway (R-HSA-70370) and its member reactions (R-HSA-9931853, R-HSA-70355, R-HSA-70361, R-HSA-70369)." no galactose_leloir_pathway Galactose catabolism (Leloir pathway) modules/galactose_leloir_pathway.yaml R-HSA-9931853 activity_evidence galm_step beta-D-galactose to alpha-D-galactose REACTION galm_activity GALM: galactose mutarotase / aldose 1-epimerase GO:0004034 aldose 1-epimerase activity UniProtKB:P0A9C3|UniProtKB:Q96C23 Aldose 1-epimerase|Galactose mutarotase GALM converts beta-D-GAL to alpha-D-GAL (human Reactome reaction) no glucose_6_phosphatase_system Glucose-6-phosphatase system (endogenous glucose production) — GSD Ia/Ib, G6PC3-SCN4 modules/glucose_6_phosphatase_system.yaml R-HSA-198513 module_evidence Reaction stoichiometries follow the human Reactome reactions R-HSA-198513 (SLC37A4 G6P:Pi exchange), R-HSA-71825 (G6PC1 liver hydrolysis) and R-HSA-3262512 (G6PC3 ubiquitous hydrolysis). yes reactome/R-HSA-198513.md SLC7A4 exchanges G6P for Pi across the ER membrane Homo sapiens glucose_6_phosphatase_system Glucose-6-phosphatase system (endogenous glucose production) — GSD Ia/Ib, G6PC3-SCN4 modules/glucose_6_phosphatase_system.yaml R-HSA-198513 activity_evidence slc37a4_step cytosolic glucose-6-phosphate + luminal Pi <-> luminal glucose-6-phosphate + cytosolic Pi REACTION slc37a4_activity SLC37A4 (G6PT): glucose-6-phosphate:phosphate antiporter GO:0061513 glucose 6-phosphate:phosphate antiporter activity UniProtKB:O43826 Glucose-6-phosphate exchanger SLC37A4 'SLC7A4 exchanges G6P for Pi across the ER membrane ' (human Reactome reaction) yes reactome/R-HSA-198513.md SLC7A4 exchanges G6P for Pi across the ER membrane Homo sapiens glucose_6_phosphatase_system Glucose-6-phosphatase system (endogenous glucose production) — GSD Ia/Ib, G6PC3-SCN4 modules/glucose_6_phosphatase_system.yaml R-HSA-3262512 activity_evidence g6pc_step luminal glucose-6-phosphate + H2O to glucose + phosphate REACTION g6pc_activity G6PC1/G6PC2/G6PC3: glucose-6-phosphatase catalytic subunit GO:0004346 glucose-6-phosphatase activity UniProtKB:P35575|UniProtKB:Q9BUM1 Glucose-6-phosphatase catalytic subunit 1|Glucose-6-phosphatase catalytic subunit 3 G6PC3 hydrolyzes G6P to form Glc and Pi (ubiquitous) (human Reactome reaction) yes reactome/R-HSA-3262512.md G6PC3 hydrolyzes G6P to form Glc and Pi (ubiquitous) Homo sapiens glucose_6_phosphatase_system Glucose-6-phosphatase system (endogenous glucose production) — GSD Ia/Ib, G6PC3-SCN4 modules/glucose_6_phosphatase_system.yaml R-HSA-71825 activity_evidence g6pc_step luminal glucose-6-phosphate + H2O to glucose + phosphate REACTION g6pc_activity G6PC1/G6PC2/G6PC3: glucose-6-phosphatase catalytic subunit GO:0004346 glucose-6-phosphatase activity UniProtKB:P35575|UniProtKB:Q9BUM1 Glucose-6-phosphatase catalytic subunit 1|Glucose-6-phosphatase catalytic subunit 3 G6PC hydrolyzes G6P to Glc and Pi (liver) (human Reactome reaction) yes reactome/R-HSA-71825.md G6PC hydrolyzes G6P to Glc and Pi (liver) Homo sapiens glycine_cleavage_system Glycine cleavage system modules/glycine_cleavage_system.yaml R-HSA-5693967 activity_evidence gcvP_reaction P-protein glycine decarboxylation REACTION gcvP_activity Glycine cleavage P protein GO:0004375 glycine dehydrogenase (decarboxylating) activity UniProtKB:P23378|UniProtKB:Q88CI9|UniProtKB:Q88P65 Glycine dehydrogenase (decarboxylating), mitochondrial|Glycine dehydrogenase (decarboxylating) 2|Glycine dehydrogenase (decarboxylating) 1 Reviewed human GLDC reaction grounding for the P-protein representative. yes reactome/R-HSA-5693967.md PXLP-K754-GLDC dimer decarboxylates Gly Homo sapiens glycine_cleavage_system Glycine cleavage system modules/glycine_cleavage_system.yaml R-HSA-5693977 activity_evidence gcvT_reaction T-protein aminomethyl transfer REACTION gcvT_activity Glycine cleavage T protein GO:0004047 aminomethyltransferase activity UniProtKB:P48728|UniProtKB:Q88CI7|UniProtKB:Q88P67 Aminomethyltransferase, mitochondrial|Aminomethyltransferase|Aminomethyltransferase Reviewed human AMT reaction grounding for the T-protein representative. yes reactome/R-HSA-5693977.md AMT transfers NH2CH2 from GCSH:SAMDLL to THF Homo sapiens glycine_cleavage_system Glycine cleavage system modules/glycine_cleavage_system.yaml R-HSA-5694018 activity_evidence gcvL_reaction L-protein dihydrolipoyl dehydrogenase reaction REACTION gcvL_activity Shared glycine-cleavage L protein GO:0004148 dihydrolipoyl dehydrogenase (NADH) activity UniProtKB:P09622|UniProtKB:Q88FB1 Dihydrolipoyl dehydrogenase, mitochondrial|Dihydrolipoyl dehydrogenase Reviewed human DLD reaction grounding for the L-protein representative. yes reactome/R-HSA-5694018.md DLD dimer:2xFAD oxidises GCSH:DHLL to GCSH:lipoate Homo sapiens glycine_cleavage_system Glycine cleavage system modules/glycine_cleavage_system.yaml R-HSA-6783984 module_evidence The human pathway supplies reviewed eukaryotic implementations of the P, H, T, and L roles, including reactions R-HSA-5693967, R-HSA-5693977, and R-HSA-5694018. yes reactome/R-HSA-6783984.md Glycine degradation Homo sapiens glycogen_biosynthesis Glycogen biosynthesis (UDP-glucose → glycogen) — GSD 0/IV/XV, UGP2-DEE modules/glycogen_biosynthesis.yaml R-HSA-3322001 activity_evidence gys_step glycogen(n) + UDP-glucose to glycogen(n+1) + UDP REACTION gys_activity GYS1/GYS2: glycogen synthase GO:0004373 alpha-1,4-glucan glucosyltransferase (UDP-glucose donor) activity UniProtKB:P13807|UniProtKB:P54840 Glycogen [starch] synthase, muscle|Glycogen [starch] synthase, liver GYS1 catalyzes the polyglucosylation of oligoGlc-GYG1 (human Reactome reaction) yes reactome/R-HSA-3322001.md GYS1 catalyzes the polyglucosylation of oligoGlc-GYG1 Homo sapiens glycogen_biosynthesis Glycogen biosynthesis (UDP-glucose → glycogen) — GSD 0/IV/XV, UGP2-DEE modules/glycogen_biosynthesis.yaml R-HSA-3322005 activity_evidence gbe1_step linear alpha-1,4-glucan to alpha-1,6-branched glycogen REACTION gbe1_activity GBE1: 1,4-alpha-glucan branching enzyme GO:0003844 1,4-alpha-glucan branching enzyme activity UniProtKB:Q04446 1,4-alpha-glucan-branching enzyme GBE1 catalyzes branch formation in polyGlc-GYG1 complexed with GYS1-a (human Reactome reaction) yes reactome/R-HSA-3322005.md GBE1 catalyzes branch formation in polyGlc-GYG1 complexed with GYS1-a Homo sapiens glycogen_biosynthesis Glycogen biosynthesis (UDP-glucose → glycogen) — GSD 0/IV/XV, UGP2-DEE modules/glycogen_biosynthesis.yaml R-HSA-3322009 activity_evidence gys_step glycogen(n) + UDP-glucose to glycogen(n+1) + UDP REACTION gys_activity GYS1/GYS2: glycogen synthase GO:0004373 alpha-1,4-glucan glucosyltransferase (UDP-glucose donor) activity UniProtKB:P13807|UniProtKB:P54840 Glycogen [starch] synthase, muscle|Glycogen [starch] synthase, liver GYS2 catalyzes the polyglucosylation of oligoGlc-GYG2 (human Reactome reaction) yes reactome/R-HSA-3322009.md GYS2 catalyzes the polyglucosylation of oligoGlc-GYG2 Homo sapiens glycogen_biosynthesis Glycogen biosynthesis (UDP-glucose → glycogen) — GSD 0/IV/XV, UGP2-DEE modules/glycogen_biosynthesis.yaml R-HSA-3322025 activity_evidence gyg1_step glycogenin + n UDP-glucose to oligoglucosyl-glycogenin primer + n UDP REACTION gyg1_activity GYG1: glycogenin (self-glucosylating initiator) GO:0008466 glycogenin glucosyltransferase activity UniProtKB:P46976 Glycogenin-1 Autoglucosylation of GYG1 complexed with GYS1-a (human Reactome reaction) yes reactome/R-HSA-3322025.md Autoglucosylation of GYG1 complexed with GYS1-a Homo sapiens glycogen_biosynthesis Glycogen biosynthesis (UDP-glucose → glycogen) — GSD 0/IV/XV, UGP2-DEE modules/glycogen_biosynthesis.yaml R-HSA-3322077 module_evidence "Step order and reaction stoichiometries follow the human Reactome ""Glycogen synthesis"" reactions R-HSA-70286 (UGP2), R-HSA-3322025 (GYG1 autoglucosylation), R-HSA-3322001 (GYS1) / R-HSA-3322009 (GYS2) and R-HSA-3322005 (GBE1 branch formation)." yes reactome/R-HSA-3322077.md Glycogen synthesis Homo sapiens glycogen_biosynthesis Glycogen biosynthesis (UDP-glucose → glycogen) — GSD 0/IV/XV, UGP2-DEE modules/glycogen_biosynthesis.yaml R-HSA-70286 activity_evidence ugp2_step glucose-1-phosphate + UTP to UDP-glucose + diphosphate REACTION ugp2_activity UGP2: UDP-glucose pyrophosphorylase GO:0003983 UTP:glucose-1-phosphate uridylyltransferase activity UniProtKB:Q16851 UTP--glucose-1-phosphate uridylyltransferase UTP + D-glucose 1-phosphate => pyrophosphate + UDP-glucose (human Reactome reaction) yes reactome/R-HSA-70286.md UTP + D-glucose 1-phosphate => pyrophosphate + UDP-glucose Homo sapiens glycogenolysis Glycogenolysis (glycogen breakdown to glucose-1/6-phosphate) — GSD III/V/VI, PGM1-CDG modules/glycogenolysis.yaml R-HSA-70221 module_evidence "Step order and reaction stoichiometries follow the human Reactome ""Glycogen breakdown (glycogenolysis)"" pathway (R-HSA-70221): phosphorolysis (R-HSA-71590), debranching (R-HSA-71552 transferase, R-HSA-71593 glucosidase) and PGM1 isomerisation (R-HSA-9638125)." yes reactome/R-HSA-70221.md Glycogen breakdown (glycogenolysis) Homo sapiens glycogenolysis Glycogenolysis (glycogen breakdown to glucose-1/6-phosphate) — GSD III/V/VI, PGM1-CDG modules/glycogenolysis.yaml R-HSA-71552 activity_evidence debranching_step limit dextrin to linear glycogen + free glucose (transferase + glucosidase) REACTION agl_activity AGL: glycogen debranching enzyme (bifunctional) GO:0004135 amylo-alpha-1,6-glucosidase activity UniProtKB:P35573 Glycogen debranching enzyme limit dextrin-glycogenin => ((1,6)-alpha-glucosyl)poly((1,4)-alpha-glucosyl) (human Reactome transferase reaction) yes reactome/R-HSA-71552.md limit dextrin-glycogenin => ((1,6)-alpha-glucosyl)poly((1,4)-alpha-glucosyl) glycogenin Homo sapiens glycogenolysis Glycogenolysis (glycogen breakdown to glucose-1/6-phosphate) — GSD III/V/VI, PGM1-CDG modules/glycogenolysis.yaml R-HSA-71590 activity_evidence phosphorylase_step glycogen(n) + phosphate to glucose-1-phosphate + glycogen(n-1) / limit dextrin REACTION phosphorylase_activity PYGL/PYGM/PYGB: glycogen phosphorylase GO:0008184 glycogen phosphorylase activity UniProtKB:P06737|UniProtKB:P11217 Glycogen phosphorylase, liver form|Glycogen phosphorylase, muscle form glycogen-glycogenin-2 + n orthophosphate => limit dextrin-glycogenin-2 (human Reactome reaction) no glycogenolysis Glycogenolysis (glycogen breakdown to glucose-1/6-phosphate) — GSD III/V/VI, PGM1-CDG modules/glycogenolysis.yaml R-HSA-71593 activity_evidence debranching_step limit dextrin to linear glycogen + free glucose (transferase + glucosidase) REACTION agl_activity AGL: glycogen debranching enzyme (bifunctional) GO:0004135 amylo-alpha-1,6-glucosidase activity UniProtKB:P35573 Glycogen debranching enzyme ((1,6)-alpha-glucosyl)poly((1,4)-alpha-glucosyl)glycogenin => poly{(1,4)-alpha-glucosyl} (human Reactome glucosidase reaction, releasing free glucose) yes reactome/R-HSA-71593.md ((1,6)-alpha-glucosyl)poly((1,4)-alpha-glucosyl)glycogenin => poly{(1,4)-alpha-glucosyl} glycogenin + alpha-D-glucose Homo sapiens glycogenolysis Glycogenolysis (glycogen breakdown to glucose-1/6-phosphate) — GSD III/V/VI, PGM1-CDG modules/glycogenolysis.yaml R-HSA-9638125 activity_evidence pgm1_step glucose-1-phosphate to glucose-6-phosphate REACTION pgm1_activity PGM1: phosphoglucomutase-1 GO:0004614 phosphoglucomutase activity UniProtKB:P36871 Phosphoglucomutase-1 PGM1:Mg2+ isomerises G1P to G6P (human Reactome reaction) no glycolysis_investment_phase Glycolysis I — investment phase (glucose → glyceraldehyde-3-phosphate); GSD VII/XII, TPI/GPI deficiency modules/glycolysis_investment_phase.yaml R-HSA-70171 module_evidence "Step order and reaction stoichiometries follow the human Reactome ""Glycolysis"" reactions R-HSA-70420 (hexokinase), R-HSA-70471 (GPI), R-HSA-70467 (PFK), R-HSA-71496 (aldolase) and R-HSA-70454 (TPI1)." yes reactome/R-HSA-70171.md Glycolysis Homo sapiens glycolysis_investment_phase Glycolysis I — investment phase (glucose → glyceraldehyde-3-phosphate); GSD VII/XII, TPI/GPI deficiency modules/glycolysis_investment_phase.yaml R-HSA-70420 activity_evidence hexokinase_step D-glucose + ATP to D-glucose-6-phosphate + ADP REACTION hexokinase_activity HK1-3/GCK: hexokinase / glucokinase GO:0004396 hexokinase activity UniProtKB:P19367|UniProtKB:P35557 Hexokinase-1|Glucokinase HK1,2,3,GCK,HKDC1 phosphorylate Glc to form G6P (human Reactome reaction) yes reactome/R-HSA-70420.md HK1,2,3,GCK,HKDC1 phosphorylate Glc to form G6P Homo sapiens glycolysis_investment_phase Glycolysis I — investment phase (glucose → glyceraldehyde-3-phosphate); GSD VII/XII, TPI/GPI deficiency modules/glycolysis_investment_phase.yaml R-HSA-70454 activity_evidence tpi_step dihydroxyacetone phosphate to D-glyceraldehyde-3-phosphate REACTION tpi_activity TPI1: triosephosphate isomerase GO:0004807 triose-phosphate isomerase activity UniProtKB:P60174 Triosephosphate isomerase TPI1 dimer isomerizes DHAP to GA3P (human Reactome reaction) yes reactome/R-HSA-70454.md TPI1 dimer isomerizes DHAP to GA3P Homo sapiens glycolysis_investment_phase Glycolysis I — investment phase (glucose → glyceraldehyde-3-phosphate); GSD VII/XII, TPI/GPI deficiency modules/glycolysis_investment_phase.yaml R-HSA-70467 activity_evidence pfk_step D-fructose-6-phosphate + ATP to D-fructose-1,6-bisphosphate + ADP REACTION pfk_activity PFKM/PFKL/PFKP: 6-phosphofructokinase-1 GO:0003872 6-phosphofructokinase activity UniProtKB:P08237 ATP-dependent 6-phosphofructokinase, muscle type PFK tetramer phosphorylates Fru(6)P (human Reactome reaction) yes reactome/R-HSA-70467.md PFK tetramer phosphorylates Fru(6)P Homo sapiens glycolysis_investment_phase Glycolysis I — investment phase (glucose → glyceraldehyde-3-phosphate); GSD VII/XII, TPI/GPI deficiency modules/glycolysis_investment_phase.yaml R-HSA-70471 activity_evidence gpi_step D-glucose-6-phosphate to D-fructose-6-phosphate REACTION gpi_activity GPI: glucose-6-phosphate isomerase GO:0004347 glucose-6-phosphate isomerase activity UniProtKB:P06744 Glucose-6-phosphate isomerase GPI dimer isomerizes G6P (human Reactome reaction) yes reactome/R-HSA-70471.md GPI dimer isomerizes G6P Homo sapiens glycolysis_investment_phase Glycolysis I — investment phase (glucose → glyceraldehyde-3-phosphate); GSD VII/XII, TPI/GPI deficiency modules/glycolysis_investment_phase.yaml R-HSA-71496 activity_evidence aldolase_step D-fructose-1,6-bisphosphate to DHAP + D-glyceraldehyde-3-phosphate REACTION aldolase_activity ALDOA/B/C: fructose-bisphosphate aldolase GO:0004332 fructose-bisphosphate aldolase activity UniProtKB:P04075 Fructose-bisphosphate aldolase A Aldolase tetramer cleaves F1,6PP (human Reactome reaction) yes reactome/R-HSA-71496.md Aldolase tetramer cleaves F1,6PP Homo sapiens glycolysis_payoff_phase Glycolysis II — payoff phase (glyceraldehyde-3-phosphate → pyruvate); PGK/PGAM/enolase/PK deficiencies modules/glycolysis_payoff_phase.yaml R-HSA-70171 module_evidence "Step order and reaction stoichiometries follow the human Reactome ""Glycolysis"" reactions R-HSA-70449 (GAPDH), R-HSA-71850 (PGK1), R-HSA-71654 (PGAM), R-HSA-71660 (enolase) and R-HSA-71670 (pyruvate kinase)." yes reactome/R-HSA-70171.md Glycolysis Homo sapiens glycolysis_payoff_phase Glycolysis II — payoff phase (glyceraldehyde-3-phosphate → pyruvate); PGK/PGAM/enolase/PK deficiencies modules/glycolysis_payoff_phase.yaml R-HSA-70449 activity_evidence gapdh_step D-glyceraldehyde-3-phosphate + NAD+ + Pi to 1,3-bisphosphoglycerate + NADH REACTION gapdh_activity GAPDH: glyceraldehyde-3-phosphate dehydrogenase GO:0004365 glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity UniProtKB:P04406 Glyceraldehyde-3-phosphate dehydrogenase GADPH tetramer dehydrogenates GA3P (human Reactome reaction) yes reactome/R-HSA-70449.md GADPH tetramer dehydrogenates GA3P Homo sapiens glycolysis_payoff_phase Glycolysis II — payoff phase (glyceraldehyde-3-phosphate → pyruvate); PGK/PGAM/enolase/PK deficiencies modules/glycolysis_payoff_phase.yaml R-HSA-71654 activity_evidence pgam_step 3-phosphoglycerate to 2-phosphoglycerate REACTION pgam_activity PGAM1/PGAM2: phosphoglycerate mutase GO:0004619 phosphoglycerate mutase activity UniProtKB:P15259 Phosphoglycerate mutase 2 PGAM dimers isomerise 3PG to 2PG (human Reactome reaction) yes reactome/R-HSA-71654.md PGAM dimers isomerise 3PG to 2PG Homo sapiens glycolysis_payoff_phase Glycolysis II — payoff phase (glyceraldehyde-3-phosphate → pyruvate); PGK/PGAM/enolase/PK deficiencies modules/glycolysis_payoff_phase.yaml R-HSA-71660 activity_evidence enolase_step 2-phosphoglycerate to phosphoenolpyruvate + H2O REACTION enolase_activity ENO1/ENO2/ENO3: enolase (phosphopyruvate hydratase) GO:0004634 phosphopyruvate hydratase activity UniProtKB:P13929 Beta-enolase Enolase dimers dehydrates 2PG (human Reactome reaction) yes reactome/R-HSA-71660.md Enolase dimers dehydrates 2PG Homo sapiens glycolysis_payoff_phase Glycolysis II — payoff phase (glyceraldehyde-3-phosphate → pyruvate); PGK/PGAM/enolase/PK deficiencies modules/glycolysis_payoff_phase.yaml R-HSA-71670 activity_evidence pk_step phosphoenolpyruvate + ADP to pyruvate + ATP REACTION pk_activity PKM/PKLR: pyruvate kinase GO:0004743 pyruvate kinase activity UniProtKB:P14618|UniProtKB:P30613 Pyruvate kinase PKM|Pyruvate kinase PKLR Pyruvate kinase dephosphorylates PEP to PYR (human Reactome reaction) yes reactome/R-HSA-71670.md Pyruvate kinase dephosphorylates PEP to PYR Homo sapiens glycolysis_payoff_phase Glycolysis II — payoff phase (glyceraldehyde-3-phosphate → pyruvate); PGK/PGAM/enolase/PK deficiencies modules/glycolysis_payoff_phase.yaml R-HSA-71850 activity_evidence pgk_step 1,3-bisphosphoglycerate + ADP to 3-phosphoglycerate + ATP REACTION pgk_activity PGK1/PGK2: phosphoglycerate kinase GO:0004618 phosphoglycerate kinase activity UniProtKB:P00558 Phosphoglycerate kinase 1 PGK complexes dephosphorylate 1,3BPG (human Reactome reaction) yes reactome/R-HSA-71850.md PGK complexes dephosphorylate 1,3BPG Homo sapiens glycosphingolipid_lysosomal_degradation Glycosphingolipid / sphingolipid lysosomal degradation to ceramide and sphingosine (the sphingolipidoses); ARSA/GALC/GBA/SMPD1/ASAH1 + GM2A/PSAP modules/glycosphingolipid_lysosomal_degradation.yaml R-HSA-1605591 activity_evidence gba_step glucosylceramide to ceramide REACTION gba_activity GBA: acid beta-glucocerebrosidase GO:0004348 glucosylceramidase activity UniProtKB:P04062 Lysosomal acid glucosylceramidase GBA1:SAPC hydrolyzes GlcCer (human Reactome reaction) yes reactome/R-HSA-1605591.md GBA1:SAPC hydrolyzes GlcCer Homo sapiens glycosphingolipid_lysosomal_degradation Glycosphingolipid / sphingolipid lysosomal degradation to ceramide and sphingosine (the sphingolipidoses); ARSA/GALC/GBA/SMPD1/ASAH1 + GM2A/PSAP modules/glycosphingolipid_lysosomal_degradation.yaml R-HSA-1606564 activity_evidence galc_step galactosylceramide to ceramide REACTION galc_activity GALC: galactosylceramidase GO:0004336 galactosylceramidase activity UniProtKB:P54803 Galactocerebrosidase GALC hydrolyzes GalCer (human Reactome reaction) yes reactome/R-HSA-1606564.md GALC hydrolyzes GalCer Homo sapiens glycosphingolipid_lysosomal_degradation Glycosphingolipid / sphingolipid lysosomal degradation to ceramide and sphingosine (the sphingolipidoses); ARSA/GALC/GBA/SMPD1/ASAH1 + GM2A/PSAP modules/glycosphingolipid_lysosomal_degradation.yaml R-HSA-1606602 activity_evidence asah1_step ceramide to sphingosine + fatty acid REACTION asah1_activity ASAH1: acid ceramidase GO:0017040 N-acylsphingosine amidohydrolase activity UniProtKB:Q13510 Acid ceramidase ASAH1 hydrolyzes ceramide (human Reactome reaction) yes reactome/R-HSA-1606602.md ASAH1 hydrolyzes ceramide Homo sapiens glycosphingolipid_lysosomal_degradation Glycosphingolipid / sphingolipid lysosomal degradation to ceramide and sphingosine (the sphingolipidoses); ARSA/GALC/GBA/SMPD1/ASAH1 + GM2A/PSAP modules/glycosphingolipid_lysosomal_degradation.yaml R-HSA-1606807 activity_evidence activator_step saposin (A-D) and GM2-activator lipid presentation REACTION psap_activity PSAP: prosaposin (saposins A-D) GO:0030290 sphingolipid activator protein activity UniProtKB:P07602 Prosaposin ARSA removes sulfate from PSAP(195-273):Sulfatide (human Reactome reaction; saposin B presents sulfatide) yes reactome/R-HSA-1606807.md ARSA removes sulfate from PSAP(195-273):Sulfatide Homo sapiens glycosphingolipid_lysosomal_degradation Glycosphingolipid / sphingolipid lysosomal degradation to ceramide and sphingosine (the sphingolipidoses); ARSA/GALC/GBA/SMPD1/ASAH1 + GM2A/PSAP modules/glycosphingolipid_lysosomal_degradation.yaml R-HSA-1606807 activity_evidence arsa_step sulfatide to galactosylceramide (3-O-desulfation) REACTION arsa_activity ARSA: arylsulfatase A / cerebroside-3-sulfatase GO:0004098 cerebroside-sulfatase activity UniProtKB:P15289 Arylsulfatase A ARSA removes sulfate from PSAP(195-273):Sulfatide (human Reactome reaction) yes reactome/R-HSA-1606807.md ARSA removes sulfate from PSAP(195-273):Sulfatide Homo sapiens glycosphingolipid_lysosomal_degradation Glycosphingolipid / sphingolipid lysosomal degradation to ceramide and sphingosine (the sphingolipidoses); ARSA/GALC/GBA/SMPD1/ASAH1 + GM2A/PSAP modules/glycosphingolipid_lysosomal_degradation.yaml R-HSA-1660661 module_evidence Step order and intermediates follow the human Reactome sphingolipid/glycosphingolipid degradation reactions R-HSA-1606807 (ARSA), R-HSA-1606564 (GALC), R-HSA-1605591 (GBA), R-HSA-9769742 (SMPD1) and R-HSA-1606602 (ASAH1). yes reactome/R-HSA-1660661.md Sphingolipid de novo biosynthesis Homo sapiens glycosphingolipid_lysosomal_degradation Glycosphingolipid / sphingolipid lysosomal degradation to ceramide and sphingosine (the sphingolipidoses); ARSA/GALC/GBA/SMPD1/ASAH1 + GM2A/PSAP modules/glycosphingolipid_lysosomal_degradation.yaml R-HSA-9769742 activity_evidence smpd1_step sphingomyelin to ceramide REACTION smpd1_activity SMPD1: acid sphingomyelinase GO:0004767 sphingomyelin phosphodiesterase activity UniProtKB:P17405 Sphingomyelin phosphodiesterase SMPD1 converts sphingomyelin to ceramide (human Reactome reaction) yes reactome/R-HSA-9769742.md SMPD1 converts sphingomyelin to ceramide Homo sapiens glyoxylate_oxalate_metabolism Glyoxylate metabolism and oxalate detoxification (the primary hyperoxalurias); AGXT/GRHPR/HOGA1/HAO1/AGXT2 modules/glyoxylate_oxalate_metabolism.yaml R-HSA-389661 module_evidence Step order and reactions follow the human Reactome glyoxylate-metabolism reactions R-HSA-389842 (HAO1), R-HSA-6784423 (HOGA1), R-HSA-389684 (AGXT), R-HSA-389826 (GRHPR) and R-HSA-904864 (AGXT2). yes reactome/R-HSA-389661.md glyoxylate_oxalate_metabolism Glyoxylate metabolism and oxalate detoxification (the primary hyperoxalurias); AGXT/GRHPR/HOGA1/HAO1/AGXT2 modules/glyoxylate_oxalate_metabolism.yaml R-HSA-389684 activity_evidence agxt_step glyoxylate + L-alanine to glycine + pyruvate REACTION agxt_activity AGXT: alanine-glyoxylate aminotransferase (peroxisomal) GO:0008453 L-alanine:glyoxylate transaminase activity UniProtKB:P21549 Serine--pyruvate aminotransferase / alanine-glyoxylate aminotransferase glyoxylate + alanine => glycine + pyruvate [peroxisome] (human Reactome reaction) yes reactome/R-HSA-389684.md glyoxylate + alanine => glycine + pyruvate [peroxisome] Homo sapiens glyoxylate_oxalate_metabolism Glyoxylate metabolism and oxalate detoxification (the primary hyperoxalurias); AGXT/GRHPR/HOGA1/HAO1/AGXT2 modules/glyoxylate_oxalate_metabolism.yaml R-HSA-389826 activity_evidence grhpr_step glyoxylate + NADPH to glycolate REACTION grhpr_activity GRHPR: glyoxylate/hydroxypyruvate reductase GO:0030267 glyoxylate reductase (NADPH) activity UniProtKB:Q9UBQ7 Glyoxylate reductase/hydroxypyruvate reductase glyoxylate + NADPH + H+ => glycolate + NADP+ (human Reactome reaction) yes reactome/R-HSA-389826.md glyoxylate + NADPH + H+ => glycolate + NADP+ Homo sapiens glyoxylate_oxalate_metabolism Glyoxylate metabolism and oxalate detoxification (the primary hyperoxalurias); AGXT/GRHPR/HOGA1/HAO1/AGXT2 modules/glyoxylate_oxalate_metabolism.yaml R-HSA-389842 activity_evidence hao1_step glycolate to glyoxylate REACTION hao1_activity HAO1: glycolate oxidase (hydroxyacid oxidase 1) GO:0003973 (S)-2-hydroxy-acid oxidase activity UniProtKB:Q9UJM8 Hydroxyacid oxidase 1 HAO1 tetramer oxidizes glycolate to glyoxylate (human Reactome reaction) yes reactome/R-HSA-389842.md HAO1 tetramer oxidizes glycolate to glyoxylate Homo sapiens glyoxylate_oxalate_metabolism Glyoxylate metabolism and oxalate detoxification (the primary hyperoxalurias); AGXT/GRHPR/HOGA1/HAO1/AGXT2 modules/glyoxylate_oxalate_metabolism.yaml R-HSA-6784423 activity_evidence hoga1_step 4-hydroxy-2-oxoglutarate to glyoxylate + pyruvate REACTION hoga1_activity HOGA1: 4-hydroxy-2-oxoglutarate aldolase GO:0008700 (R,S)-4-hydroxy-2-oxoglutarate aldolase activity UniProtKB:Q86XE5 4-hydroxy-2-oxoglutarate aldolase, mitochondrial HOGA1 tetramer aldol-cleaves 4-OH-2-oxoglutarate (HOG) to glyoxylate and pyruvate (human Reactome reaction) yes reactome/R-HSA-6784423.md HOGA1 tetramer aldol-cleaves 4-OH-2-oxoglutarate (HOG) to glyoxylate and pyruvate Homo sapiens glyoxylate_oxalate_metabolism Glyoxylate metabolism and oxalate detoxification (the primary hyperoxalurias); AGXT/GRHPR/HOGA1/HAO1/AGXT2 modules/glyoxylate_oxalate_metabolism.yaml R-HSA-904864 activity_evidence agxt2_step glyoxylate transamination to glycine (mitochondrial) REACTION agxt2_activity AGXT2: alanine-glyoxylate aminotransferase 2 (mitochondrial) GO:0008453 L-alanine:glyoxylate transaminase activity UniProtKB:Q9BYV1 Alanine--glyoxylate aminotransferase 2, mitochondrial Mitochondrial AGXT2 tetramer transaminates glyoxylate and beta-aminoisobutyrate (human Reactome reaction) yes reactome/R-HSA-904864.md Mitochondrial AGXT2 tetramer transaminates glyoxylate and alanine to glycine and pyruvate Homo sapiens gpi_anchor_core_glycan_assembly GPI anchor biosynthesis II — de-N-acetylation, inositol acylation and mannosylation; PIGL/PIGW/PIGM/PIGX/PIGV/PIGB modules/gpi_anchor_core_glycan_assembly.yaml R-HSA-162683 activity_evidence pigw_step GlcN-PI to GlcN-(acyl)PI REACTION pigw_activity PIGW: GPI inositol acyltransferase GO:0032216 glucosaminyl-phosphatidylinositol O-acyltransferase activity UniProtKB:Q7Z7B1 Phosphatidylinositol-glycan biosynthesis class W protein glucosaminyl-PI + fatty acyl-CoA -> glucosaminyl-acyl-PI + CoA (human Reactome reaction) yes reactome/R-HSA-162683.md glucosaminyl-PI + fatty acyl-CoA -> glucosaminyl-acyl-PI + CoA-SH Homo sapiens gpi_anchor_core_glycan_assembly GPI anchor biosynthesis II — de-N-acetylation, inositol acylation and mannosylation; PIGL/PIGW/PIGM/PIGX/PIGV/PIGB modules/gpi_anchor_core_glycan_assembly.yaml R-HSA-162710 module_evidence "Step order and intermediates follow the human Reactome ""Synthesis of glycosylphosphatidylinositol (GPI)"" sub-pathway (reactions R-HSA-162857/162683/162830/162873/162821)." yes reactome/R-HSA-162710.md Synthesis of glycosylphosphatidylinositol (GPI) Homo sapiens gpi_anchor_core_glycan_assembly GPI anchor biosynthesis II — de-N-acetylation, inositol acylation and mannosylation; PIGL/PIGW/PIGM/PIGX/PIGV/PIGB modules/gpi_anchor_core_glycan_assembly.yaml R-HSA-162821 activity_evidence pigb_step Man2-GlcN-(acyl)PI to Man3-GlcN-(acyl)PI REACTION pigb_activity PIGB: GPI mannosyltransferase III GO:0120564 dol-P-Man:Man(2)GlcN-acyl-PI alpha-1,2-mannosyltransferase activity UniProtKB:Q92521 GPI mannosyltransferase 3 mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI + dolichol phosphate D-mannose -> ... (human Reactome reaction) yes reactome/R-HSA-162821.md mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI + dolichol phosphate D-mannose -> mannose (a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI + dolichol phosphate Homo sapiens gpi_anchor_core_glycan_assembly GPI anchor biosynthesis II — de-N-acetylation, inositol acylation and mannosylation; PIGL/PIGW/PIGM/PIGX/PIGV/PIGB modules/gpi_anchor_core_glycan_assembly.yaml R-HSA-162830 activity_evidence gpi_mt1_step GlcN-(acyl)PI to Man1-GlcN-(acyl)PI PROTEIN_COMPLEX pigm_activity PIGM: GPI mannosyltransferase I (catalytic) GO:0180041 dol-P-Man:GlcN-acyl-PI alpha-1,4-mannosyltransferase activity UniProtKB:Q9H3S5 GPI mannosyltransferase 1 glucosaminyl-acyl-PI + dolichol phosphate D-mannose -> mannosyl-glucosaminyl-acyl-PI (human Reactome reaction) yes reactome/R-HSA-162830.md glucosaminyl-acyl-PI + dolichol phosphate D-mannose -> mannose(al1-4)glucosaminyl-acyl-PI + dolichol phosphate Homo sapiens gpi_anchor_core_glycan_assembly GPI anchor biosynthesis II — de-N-acetylation, inositol acylation and mannosylation; PIGL/PIGW/PIGM/PIGX/PIGV/PIGB modules/gpi_anchor_core_glycan_assembly.yaml R-HSA-162857 activity_evidence pigl_step GlcNAc-PI to glucosaminyl-PI (GlcN-PI) REACTION pigl_activity PIGL: GlcNAc-PI de-N-acetylase GO:0000225 N-acetylglucosaminylphosphatidylinositol deacetylase activity UniProtKB:Q9Y2B2 N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase N-acetylglucosaminyl-PI + H2O -> glucosaminyl-PI + acetate (human Reactome reaction) yes reactome/R-HSA-162857.md N-acetylglucosaminyl-PI + H2O -> glucosaminyl-PI + acetate Homo sapiens gpi_anchor_core_glycan_assembly GPI anchor biosynthesis II — de-N-acetylation, inositol acylation and mannosylation; PIGL/PIGW/PIGM/PIGX/PIGV/PIGB modules/gpi_anchor_core_glycan_assembly.yaml R-HSA-162873 activity_evidence pigv_step Man1-GlcN-(acyl)PI to Man2-GlcN-(acyl)PI REACTION pigv_activity PIGV: GPI mannosyltransferase II GO:0120563 dol-P-Man:Man(1)GlcN-acyl-PI alpha-1,6-mannosyltransferase activity UniProtKB:Q9NUD9 GPI mannosyltransferase 2 (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI + dolichol phosphate D-mannose -> ... (human Reactome reaction) yes reactome/R-HSA-162873.md (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI + dolichol phosphate D-mannose -> mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI + dolichol phosphate Homo sapiens gpi_anchor_ethanolamine_phosphate GPI anchor biosynthesis III — ethanolamine-phosphate additions; PIGN/PIGG/PIGF/PIGO modules/gpi_anchor_ethanolamine_phosphate.yaml R-HSA-162710 module_evidence "Step order and intermediates follow the human Reactome ""Synthesis of glycosylphosphatidylinositol (GPI)"" sub-pathway (reactions R-HSA-162798 PIGN, R-HSA-162742 PIGG)." yes reactome/R-HSA-162710.md Synthesis of glycosylphosphatidylinositol (GPI) Homo sapiens gpi_anchor_ethanolamine_phosphate GPI anchor biosynthesis III — ethanolamine-phosphate additions; PIGN/PIGG/PIGF/PIGO modules/gpi_anchor_ethanolamine_phosphate.yaml R-HSA-162710 activity_evidence pigo_step bridging ethanolamine-phosphate added to mannose-III PROTEIN_COMPLEX pigo_activity PIGO: GPI ethanolamine phosphate transferase 3 (catalytic) GO:0051377 mannose-ethanolamine phosphotransferase activity UniProtKB:Q8TEQ8 GPI ethanolamine phosphate transferase 3 Synthesis of glycosylphosphatidylinositol (GPI) (human Reactome pathway) yes reactome/R-HSA-162710.md Synthesis of glycosylphosphatidylinositol (GPI) Homo sapiens gpi_anchor_ethanolamine_phosphate GPI anchor biosynthesis III — ethanolamine-phosphate additions; PIGN/PIGG/PIGF/PIGO modules/gpi_anchor_ethanolamine_phosphate.yaml R-HSA-162742 activity_evidence pigg_step ethanolamine-phosphate added to mannose-II PROTEIN_COMPLEX pigg_activity PIGG: GPI ethanolamine phosphate transferase 2 (catalytic) GO:0051377 mannose-ethanolamine phosphotransferase activity UniProtKB:Q5H8A4 GPI ethanolamine phosphate transferase 2 (ethanolamineP) mannose (a1-2) mannose (a1-6) (ethanolamineP) ... (human Reactome reaction) yes reactome/R-HSA-162742.md (ethanolamineP) mannose (a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI -> (ethanolamineP) mannose (a1-2) (ethanolamineP) mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI Homo sapiens gpi_anchor_ethanolamine_phosphate GPI anchor biosynthesis III — ethanolamine-phosphate additions; PIGN/PIGG/PIGF/PIGO modules/gpi_anchor_ethanolamine_phosphate.yaml R-HSA-162798 activity_evidence pign_step ethanolamine-phosphate added to mannose-I REACTION pign_activity PIGN: GPI ethanolamine phosphate transferase 1 GO:0051377 mannose-ethanolamine phosphotransferase activity UniProtKB:O95427 GPI ethanolamine phosphate transferase 1 mannose(a1-4)glucosaminyl-acyl-PI + phosphatidylethanolamine -> ... (human Reactome reaction) yes reactome/R-HSA-162798.md mannose(a1-4)glucosaminyl-acyl-PI + phosphatidylethanolamine -> (ethanolamineP) mannose(al1-4)glucosaminyl-acyl-PI + diacylglycerol Homo sapiens gpi_anchor_glcnac_transferase GPI anchor biosynthesis I — GlcNAc transferase (GPI-GnT) complex; PIGA/PIGC/PIGH/PIGP/PIGQ/PIGY modules/gpi_anchor_glcnac_transferase.yaml R-HSA-162710 module_evidence "The GlcNAc-PI-forming reaction follows the human Reactome ""Synthesis of glycosylphosphatidylinositol (GPI)"" sub-pathway (reaction R-HSA-162730)." yes reactome/R-HSA-162710.md Synthesis of glycosylphosphatidylinositol (GPI) Homo sapiens gpi_anchor_glcnac_transferase GPI anchor biosynthesis I — GlcNAc transferase (GPI-GnT) complex; PIGA/PIGC/PIGH/PIGP/PIGQ/PIGY modules/gpi_anchor_glcnac_transferase.yaml R-HSA-162730 activity_evidence gpi_gnt_step phosphatidylinositol + UDP-GlcNAc to GlcNAc-PI PROTEIN_COMPLEX piga_activity PIGA: catalytic GlcNAc transferase subunit GO:0017176 phosphatidylinositol N-acetylglucosaminyltransferase activity UniProtKB:P37287 Phosphatidylinositol N-acetylglucosaminyltransferase subunit A phosphatidylinositol + UDP-N-acetyl-D-glucosamine -> N-acetylglucosaminyl-phosphatidylinositol + UDP (human Reactome reaction) yes reactome/R-HSA-162730.md phosphatidylinositol + UDP-N-acetyl-D-glucosamine -> N-acetylglucosaminyl-PI + UDP Homo sapiens gpi_anchor_remodeling GPI anchor biosynthesis V — post-attachment lipid remodeling; PGAP1/PGAP3/PGAP2 modules/gpi_anchor_remodeling.yaml R-HSA-162710 module_evidence "The inositol-deacylation step (PGAP1) follows the human Reactome reaction R-HSA-162729 (uPAR-acyl-GPI + H2O -> uPAR + long-chain fatty acid), part of ""Synthesis of GPI""." yes reactome/R-HSA-162710.md Synthesis of glycosylphosphatidylinositol (GPI) Homo sapiens gpi_anchor_remodeling GPI anchor biosynthesis V — post-attachment lipid remodeling; PGAP1/PGAP3/PGAP2 modules/gpi_anchor_remodeling.yaml R-HSA-162729 activity_evidence pgap1_step removal of the inositol-linked acyl chain from the GPI anchor REACTION pgap1_activity PGAP1: GPI inositol-deacylase GO:0160215 deacylase activity UniProtKB:Q75T13 GPI inositol-deacylase uPAR-acyl-GPI + H2O -> uPAR + long-chain fatty acid (human Reactome reaction) yes reactome/R-HSA-162729.md uPAR-acyl-GPI + H2O -> uPAR + long-chain fatty acid Homo sapiens gpi_anchor_transamidase GPI anchor biosynthesis IV — transamidase complex (attachment to protein); PIGK/PIGS/PIGT/PIGU/GPAA1 modules/gpi_anchor_transamidase.yaml R-HSA-162791 module_evidence "The transamidation reaction follows the human Reactome ""Attachment of GPI anchor to uPAR"" reaction (a representative GPI-T substrate), part of ""Synthesis of GPI"" (R-HSA-162710)." yes reactome/R-HSA-162791.md Attachment of GPI anchor to uPAR Homo sapiens gpi_anchor_transamidase GPI anchor biosynthesis IV — transamidase complex (attachment to protein); PIGK/PIGS/PIGT/PIGU/GPAA1 modules/gpi_anchor_transamidase.yaml R-HSA-162791 activity_evidence gpi_transamidase_step transfer of the completed GPI anchor onto the protein C-terminus PROTEIN_COMPLEX pigk_activity PIGK (GPI8): catalytic transamidase subunit GO:0003923 GPI-anchor transamidase activity UniProtKB:Q92643 GPI-anchor transamidase Attachment of GPI anchor to uPAR (human Reactome reaction) yes reactome/R-HSA-162791.md Attachment of GPI anchor to uPAR Homo sapiens heme_biosynthesis Heme B biosynthesis through alternative entry and oxidation routes modules/heme_biosynthesis.yaml R-HSA-189451 module_evidence Reactome supports one concrete metazoan realization using C4 entry, CPOX, and PPOX; human proteins are exemplars rather than route-level taxon or localization constraints. yes reactome/R-HSA-189451.md Heme biosynthesis Homo sapiens heparan_sulfate_lysosomal_degradation Heparan sulfate lysosomal degradation (the mucopolysaccharidoses); IDS/IDUA/SGSH/HGSNAT/NAGLU/GNS/GUSB modules/heparan_sulfate_lysosomal_degradation.yaml R-HSA-1638032 activity_evidence gns_step removal of 6-O-sulfate from terminal GlcNAc-6-sulfate REACTION gns_activity GNS: N-acetylglucosamine-6-sulfatase GO:0008449 N-acetylglucosamine-6-sulfatase activity UniProtKB:P15586 N-acetylglucosamine-6-sulfatase GNS:Ca2+ cleaves sulfate from GlcNAc-6-sulfate units of keratan/heparan sulfate (human Reactome reaction) yes reactome/R-HSA-1638032.md GNS:Ca2+ cleaves sulfate from GlcNAc-6-sulfate units of keratan sulfate Homo sapiens heparan_sulfate_lysosomal_degradation Heparan sulfate lysosomal degradation (the mucopolysaccharidoses); IDS/IDUA/SGSH/HGSNAT/NAGLU/GNS/GUSB modules/heparan_sulfate_lysosomal_degradation.yaml R-HSA-1678650 activity_evidence ids_step removal of 2-O-sulfate from terminal iduronate-2-sulfate REACTION ids_activity IDS: iduronate-2-sulfatase GO:0004423 iduronate-2-sulfatase activity UniProtKB:P22304 Iduronate 2-sulfatase IDS hydrolyses Heparan sulfate chain(5) (human Reactome reaction) yes reactome/R-HSA-1678650.md IDS hydrolyses Heparan sulfate chain(5) Homo sapiens heparan_sulfate_lysosomal_degradation Heparan sulfate lysosomal degradation (the mucopolysaccharidoses); IDS/IDUA/SGSH/HGSNAT/NAGLU/GNS/GUSB modules/heparan_sulfate_lysosomal_degradation.yaml R-HSA-1678660 activity_evidence hgsnat_step N-acetylation of terminal alpha-glucosamine (from acetyl-CoA) REACTION hgsnat_activity HGSNAT: heparan-alpha-glucosaminide N-acetyltransferase GO:0015019 heparan-alpha-glucosaminide N-acetyltransferase activity UniProtKB:Q68CP4 Heparan-alpha-glucosaminide N-acetyltransferase HGSNAT oligomer acetylates Heparan sulfate chain(3) (human Reactome reaction) yes reactome/R-HSA-1678660.md HGSNAT oligomer acetylates Heparan sulfate chain(3) Homo sapiens heparan_sulfate_lysosomal_degradation Heparan sulfate lysosomal degradation (the mucopolysaccharidoses); IDS/IDUA/SGSH/HGSNAT/NAGLU/GNS/GUSB modules/heparan_sulfate_lysosomal_degradation.yaml R-HSA-1678708 activity_evidence sgsh_step removal of N-sulfate from terminal N-sulfoglucosamine REACTION sgsh_activity SGSH: sulfamidase (heparan-N-sulfatase) GO:0016250 N-sulfoglucosamine sulfohydrolase activity UniProtKB:P51688 N-sulphoglucosamine sulphohydrolase SGSH hydrolyses Heparan sulfate chain(2) (human Reactome reaction) yes reactome/R-HSA-1678708.md SGSH hydrolyses Heparan sulfate chain(2) Homo sapiens heparan_sulfate_lysosomal_degradation Heparan sulfate lysosomal degradation (the mucopolysaccharidoses); IDS/IDUA/SGSH/HGSNAT/NAGLU/GNS/GUSB modules/heparan_sulfate_lysosomal_degradation.yaml R-HSA-1678716 activity_evidence idua_step hydrolysis of terminal alpha-L-iduronate REACTION idua_activity IDUA: alpha-L-iduronidase GO:0003940 L-iduronidase activity UniProtKB:P35475 Alpha-L-iduronidase IDUA cleaves iduronate from HS chain (human Reactome reaction) yes reactome/R-HSA-1678716.md IDUA cleaves iduronate from HS chain Homo sapiens heparan_sulfate_lysosomal_degradation Heparan sulfate lysosomal degradation (the mucopolysaccharidoses); IDS/IDUA/SGSH/HGSNAT/NAGLU/GNS/GUSB modules/heparan_sulfate_lysosomal_degradation.yaml R-HSA-1678742 activity_evidence naglu_step hydrolysis of terminal alpha-N-acetylglucosamine REACTION naglu_activity NAGLU: alpha-N-acetylglucosaminidase GO:0004561 alpha-N-acetylglucosaminidase activity UniProtKB:P54802 Alpha-N-acetylglucosaminidase NAGLU hydrolyses Heparan sulfate chain(4) (human Reactome reaction) yes reactome/R-HSA-1678742.md NAGLU hydrolyses Heparan sulfate chain(4) Homo sapiens heparan_sulfate_lysosomal_degradation Heparan sulfate lysosomal degradation (the mucopolysaccharidoses); IDS/IDUA/SGSH/HGSNAT/NAGLU/GNS/GUSB modules/heparan_sulfate_lysosomal_degradation.yaml R-HSA-1678854 activity_evidence gusb_step hydrolysis of terminal beta-D-glucuronate REACTION gusb_activity GUSB: beta-glucuronidase GO:0004566 beta-glucuronidase activity UniProtKB:P08236 Beta-glucuronidase GUSB tetramer hydrolyses CS/HS precursor (human Reactome reaction) yes reactome/R-HSA-1678854.md GUSB tetramer hydrolyses CS/HS precursor Homo sapiens heparan_sulfate_lysosomal_degradation Heparan sulfate lysosomal degradation (the mucopolysaccharidoses); IDS/IDUA/SGSH/HGSNAT/NAGLU/GNS/GUSB modules/heparan_sulfate_lysosomal_degradation.yaml R-HSA-2024096 module_evidence "Step order and intermediates follow the human Reactome ""HS-GAG degradation"" pathway (reactions R-HSA-1678650/1678716/1678708/1678660/1678742/1638032/1678854)." yes reactome/R-HSA-2024096.md HS-GAG degradation Homo sapiens homocysteine_metabolism Homocysteine metabolism (remethylation and transsulfuration) modules/homocysteine_metabolism.yaml R-HSA-1614524 activity_evidence cbs_step L-homocysteine + L-serine to L-cystathionine REACTION cbs_activity CBS: cystathionine beta-synthase GO:0004122 cystathionine beta-synthase activity UniProtKB:P35520 Cystathionine beta-synthase PXLP-CBS tetramers condenses HCYS and L-Ser to form L-Cystathionine (human Reactome reaction) yes reactome/R-HSA-1614524.md PXLP-CBS tetramers condenses HCYS and L-Ser to form L-Cystathionine Homo sapiens homocysteine_metabolism Homocysteine metabolism (remethylation and transsulfuration) modules/homocysteine_metabolism.yaml R-HSA-1614583 activity_evidence cth_step L-cystathionine to L-cysteine + 2-oxobutanoate + NH3 REACTION cth_activity CTH/CSE: cystathionine gamma-lyase GO:0004123 cystathionine gamma-lyase activity UniProtKB:P32929 Cystathionine gamma-lyase PXLP-K212-CTH cleaves L-Cystathionine (human Reactome reaction) no homocysteine_metabolism Homocysteine metabolism (remethylation and transsulfuration) modules/homocysteine_metabolism.yaml R-HSA-1614635 module_evidence Step order and reaction stoichiometries follow the human Reactome sulfur amino acid / methionine-cycle reactions: R-HSA-200676 (MTHFR), R-HSA-3149539 (MTR), R-HSA-1614524 (CBS) and R-HSA-1614583 (CTH). yes reactome/R-HSA-1614635.md Sulfur amino acid metabolism Homo sapiens homocysteine_metabolism Homocysteine metabolism (remethylation and transsulfuration) modules/homocysteine_metabolism.yaml R-HSA-200676 activity_evidence mthfr_step 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate REACTION mthfr_activity MTHFR: methylenetetrahydrofolate reductase GO:0004489 methylenetetrahydrofolate reductase [NAD(P)H] activity UniProtKB:P42898 Methylenetetrahydrofolate reductase MTHFR dimer reduces 5,10-methylene-THFPG to 5-methyl-THFPG (human Reactome reaction) no homocysteine_metabolism Homocysteine metabolism (remethylation and transsulfuration) modules/homocysteine_metabolism.yaml R-HSA-3149539 activity_evidence mtr_step L-homocysteine + 5-methyl-THF to L-methionine + THF REACTION mtr_activity MTR: methionine synthase (methylcobalamin-dependent) GO:0008705 methionine synthase activity UniProtKB:Q99707 Methionine synthase MTR transfers CH3 group from 5-methyl-THF to cob(I)alamin (human Reactome reaction) no keratan_chondroitin_sulfate_lysosomal_degradation Keratan and chondroitin sulfate lysosomal degradation (Morquio / GM2); GALNS/GLB1/HEXA/HEXB modules/keratan_chondroitin_sulfate_lysosomal_degradation.yaml R-HSA-1630304 activity_evidence galns_step removal of 6-O-sulfate from terminal galactose-6-sulfate / GalNAc-6-sulfate REACTION galns_activity GALNS: N-acetylgalactosamine-6-sulfatase / galactose-6-sulfatase GO:0043890 N-acetylgalactosamine-6-sulfatase activity UniProtKB:P34059 N-acetylgalactosamine-6-sulfatase GALNS oligomer hydrolyses sulfate from Gal6S in keratan sulfate (human Reactome reaction) yes reactome/R-HSA-1630304.md GALNS oligomer hydrolyses sulfate from Gal6S in keratan sulfate Homo sapiens keratan_chondroitin_sulfate_lysosomal_degradation Keratan and chondroitin sulfate lysosomal degradation (Morquio / GM2); GALNS/GLB1/HEXA/HEXB modules/keratan_chondroitin_sulfate_lysosomal_degradation.yaml R-HSA-1630306 activity_evidence glb1_step hydrolysis of terminal beta-D-galactose REACTION glb1_activity GLB1: lysosomal acid beta-galactosidase GO:0004565 beta-galactosidase activity UniProtKB:P16278 Beta-galactosidase GLB1 hydrolyses a glycosaminoglycan (human Reactome reaction) yes reactome/R-HSA-1630306.md GLB1 hydrolyses a glycosaminoglycan Homo sapiens keratan_chondroitin_sulfate_lysosomal_degradation Keratan and chondroitin sulfate lysosomal degradation (Morquio / GM2); GALNS/GLB1/HEXA/HEXB modules/keratan_chondroitin_sulfate_lysosomal_degradation.yaml R-HSA-1638053 activity_evidence hex_step hydrolysis of terminal beta-N-acetylhexosamine PROTEIN_COMPLEX hexa_activity HEXA: beta-hexosaminidase alpha subunit GO:0004563 beta-N-acetylhexosaminidase activity UniProtKB:P06865 Beta-hexosaminidase subunit alpha HEXA cleaves the terminal GlcNAc from keratan sulfate (human Reactome reaction) yes reactome/R-HSA-1638053.md HEXA cleaves the terminal GlcNAc from keratan sulfate Homo sapiens keratan_chondroitin_sulfate_lysosomal_degradation Keratan and chondroitin sulfate lysosomal degradation (Morquio / GM2); GALNS/GLB1/HEXA/HEXB modules/keratan_chondroitin_sulfate_lysosomal_degradation.yaml R-HSA-1638053 activity_evidence hex_step hydrolysis of terminal beta-N-acetylhexosamine PROTEIN_COMPLEX hexb_activity HEXB: beta-hexosaminidase beta subunit GO:0004563 beta-N-acetylhexosaminidase activity UniProtKB:P07686 Beta-hexosaminidase subunit beta HEXA cleaves the terminal GlcNAc from keratan sulfate (human Reactome reaction; HexA = HEXA:HEXB) yes reactome/R-HSA-1638053.md HEXA cleaves the terminal GlcNAc from keratan sulfate Homo sapiens keratan_chondroitin_sulfate_lysosomal_degradation Keratan and chondroitin sulfate lysosomal degradation (Morquio / GM2); GALNS/GLB1/HEXA/HEXB modules/keratan_chondroitin_sulfate_lysosomal_degradation.yaml R-HSA-2024096 module_evidence The keratan/chondroitin sulfate exolytic steps follow the human Reactome GAG-degradation reactions R-HSA-1630304 (GALNS), R-HSA-1630306 (GLB1) and R-HSA-1638053 (HEXA/HEXB). yes reactome/R-HSA-2024096.md HS-GAG degradation Homo sapiens ketogenesis Ketogenesis (hepatic ketone body synthesis) modules/ketogenesis.yaml R-HSA-73912 activity_evidence bdh1_step acetoacetate + NADH to (R)-3-hydroxybutyrate + NAD+ REACTION bdh1_activity BDH1: D-3-hydroxybutyrate dehydrogenase GO:0003858 3-hydroxybutyrate dehydrogenase activity UniProtKB:Q02338 D-beta-hydroxybutyrate dehydrogenase, mitochondrial acetoacetic acid + NADH + H+ <=> beta-hydroxybutyrate + NAD+ (human Reactome reaction) no ketogenesis Ketogenesis (hepatic ketone body synthesis) modules/ketogenesis.yaml R-HSA-73916 activity_evidence acat1_step 2 acetyl-CoA to acetoacetyl-CoA + CoA REACTION acat1_activity ACAT1: acetyl-CoA acetyltransferase (thiolase) GO:0003985 acetyl-CoA C-acetyltransferase activity UniProtKB:P24752 Acetyl-CoA acetyltransferase, mitochondrial 2 acetyl-CoA <=> acetoacetyl-CoA + CoA (human Reactome reaction) yes reactome/R-HSA-73916.md 2 acetyl-CoA <=> acetoacetyl-CoA + CoA Homo sapiens ketogenesis Ketogenesis (hepatic ketone body synthesis) modules/ketogenesis.yaml R-HSA-73918 activity_evidence hmgcs2_step acetoacetyl-CoA + acetyl-CoA to HMG-CoA + CoA REACTION hmgcs2_activity HMGCS2: mitochondrial HMG-CoA synthase GO:0004421 hydroxymethylglutaryl-CoA synthase activity UniProtKB:P54868 Hydroxymethylglutaryl-CoA synthase, mitochondrial acetoacetyl-CoA+acetyl-CoA => HMG-CoA + CoASH (human Reactome reaction) no ketogenesis Ketogenesis (hepatic ketone body synthesis) modules/ketogenesis.yaml R-HSA-74180 activity_evidence hmgcl_step HMG-CoA to acetoacetate + acetyl-CoA REACTION hmgcl_activity HMGCL: HMG-CoA lyase GO:0004419 hydroxymethylglutaryl-CoA lyase activity UniProtKB:P35914 Hydroxymethylglutaryl-CoA lyase, mitochondrial HMG CoA => acetoacetic acid + acetyl CoA (human Reactome reaction) no ketogenesis Ketogenesis (hepatic ketone body synthesis) modules/ketogenesis.yaml R-HSA-77111 module_evidence "Step order and reaction stoichiometries follow the human Reactome ""Synthesis of Ketone Bodies"" pathway (R-HSA-77111): R-HSA-73916 (ACAT1), R-HSA-73918 (HMGCS2), R-HSA-74180 (HMGCL) and R-HSA-73912 (BDH1)." yes reactome/R-HSA-77111.md Synthesis of Ketone Bodies Homo sapiens lactate_fermentation_and_bpg_shunt Lactate fermentation and the Rapoport-Luebering (2,3-BPG) shunt — GSD XI, BPGM deficiency modules/lactate_fermentation_and_bpg_shunt.yaml R-HSA-6798335 activity_evidence bpgm_step 1,3-bisphosphoglycerate to 2,3-bisphosphoglycerate REACTION bpgm_activity BPGM: bisphosphoglycerate mutase GO:0004082 bisphosphoglycerate mutase activity UniProtKB:P07738 Bisphosphoglycerate mutase BPGM dimer isomerises 1,3BPG to 2,3BPG (human Reactome reaction) yes reactome/R-HSA-6798335.md BPGM dimer isomerises 1,3BPG to 2,3BPG Homo sapiens lactate_fermentation_and_bpg_shunt Lactate fermentation and the Rapoport-Luebering (2,3-BPG) shunt — GSD XI, BPGM deficiency modules/lactate_fermentation_and_bpg_shunt.yaml R-HSA-71849 module_evidence Reactions follow the human Reactome reactions R-HSA-71849 (LDH pyruvate -> lactate) and R-HSA-6798335 (BPGM 1,3-BPG -> 2,3-BPG). yes reactome/R-HSA-71849.md LDH tetramer reduces PYR to LACT Homo sapiens lactate_fermentation_and_bpg_shunt Lactate fermentation and the Rapoport-Luebering (2,3-BPG) shunt — GSD XI, BPGM deficiency modules/lactate_fermentation_and_bpg_shunt.yaml R-HSA-71849 activity_evidence ldh_step pyruvate + NADH to L-lactate + NAD+ REACTION ldh_activity LDHA/LDHB: L-lactate dehydrogenase GO:0004459 L-lactate dehydrogenase (NAD+) activity UniProtKB:P00338|UniProtKB:P07195 L-lactate dehydrogenase A chain|L-lactate dehydrogenase B chain LDH tetramer reduces PYR to LACT (human Reactome reaction) yes reactome/R-HSA-71849.md LDH tetramer reduces PYR to LACT Homo sapiens leucine_catabolism Distal L-leucine catabolism modules/leucine_catabolism.yaml R-HSA-70895 module_evidence Human Reactome provides a curated instance of the ordered distal reactions, while the module abstracts away mitochondrial localization. yes reactome/R-HSA-70895.md Branched-chain amino acid catabolism Homo sapiens lysine_catabolism L-lysine catabolism (saccharopine pathway to glutaryl-CoA; glutaric aciduria type 1) modules/lysine_catabolism.yaml R-HSA-71046 activity_evidence gcdh_step glutaryl-CoA + FAD to crotonyl-CoA + CO2 + FADH2 REACTION gcdh_activity GCDH: glutaryl-CoA dehydrogenase GO:0004361 glutaryl-CoA dehydrogenase activity UniProtKB:Q92947 Glutaryl-CoA dehydrogenase, mitochondrial glutaryl-CoA + FAD => crotonyl-CoA + FADH2 + CO2 (human Reactome reaction) no lysine_catabolism L-lysine catabolism (saccharopine pathway to glutaryl-CoA; glutaric aciduria type 1) modules/lysine_catabolism.yaml R-HSA-71064 module_evidence "Step order follows the human Reactome ""Lysine catabolism"" pathway; the glutaryl-CoA-forming (R-HSA-9858590, DLST) and glutaryl-CoA dehydrogenase (R-HSA-71046, GCDH) reactions were verified against the local cache." yes reactome/R-HSA-71064.md Lysine catabolism Homo sapiens lysine_catabolism L-lysine catabolism (saccharopine pathway to glutaryl-CoA; glutaric aciduria type 1) modules/lysine_catabolism.yaml R-HSA-9858590 activity_evidence oadhc_step 2-oxoadipate + CoA + NAD+ to glutaryl-CoA + CO2 + NADH PROTEIN_COMPLEX dlst_e2 DLST: shared E2 (glutaryltransferase core) GO:0120571 dihydrolipoyllysine-residue glutaryltransferase activity UniProtKB:P36957 Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial DLST transfers glutaryl to CoA (human Reactome reaction) no lysosomal_glycogen_degradation Lysosomal glycogen degradation (acid alpha-glucosidase) — Pompe disease (GSD II) modules/lysosomal_glycogen_degradation.yaml R-HSA-9036727 module_evidence The reaction follows the human Reactome reaction R-HSA-9036727 (GAA hydrolyzes lysosomal glycogen). yes reactome/R-HSA-9036727.md GAA hydrolyzes lysosomal glycogen Homo sapiens lysosomal_glycogen_degradation Lysosomal glycogen degradation (acid alpha-glucosidase) — Pompe disease (GSD II) modules/lysosomal_glycogen_degradation.yaml R-HSA-9036727 activity_evidence gaa_step glycogen + n H2O to n D-glucose (acidic lysosomal pH) REACTION gaa_activity GAA: lysosomal acid alpha-glucosidase (acid maltase) GO:0004558 alpha-1,4-glucosidase activity UniProtKB:P10253 Lysosomal alpha-glucosidase GAA hydrolyzes lysosomal glycogen (human Reactome reaction) yes reactome/R-HSA-9036727.md GAA hydrolyzes lysosomal glycogen Homo sapiens mevalonate_pathway Mevalonate pathway (acetyl-CoA -> isopentenyl diphosphate); statin target, mevalonate kinase deficiency modules/mevalonate_pathway.yaml R-HSA-191273 module_evidence Step order and reaction stoichiometries follow the human Reactome cholesterol/ isoprenoid-biosynthesis reactions R-HSA-191323 (HMGCS1), R-HSA-191352 (HMGCR), R-HSA-191380 (MVK), R-HSA-191422 (PMVK) and R-HSA-191414 (MVD). yes reactome/R-HSA-191273.md Cholesterol biosynthesis Homo sapiens mevalonate_pathway Mevalonate pathway (acetyl-CoA -> isopentenyl diphosphate); statin target, mevalonate kinase deficiency modules/mevalonate_pathway.yaml R-HSA-191323 activity_evidence hmgcs1_step acetoacetyl-CoA + acetyl-CoA to (S)-HMG-CoA + CoA REACTION hmgcs1_activity HMGCS1: HMG-CoA synthase (cytosolic) GO:0004421 hydroxymethylglutaryl-CoA synthase activity UniProtKB:Q01581 Hydroxymethylglutaryl-CoA synthase, cytoplasmic HMGCS1 condenses Ac-CoA and ACA-CoA to form bHMG-CoA (human Reactome reaction) yes reactome/R-HSA-191323.md HMGCS1 condenses Ac-CoA and ACA-CoA to form bHMG-CoA Homo sapiens mevalonate_pathway Mevalonate pathway (acetyl-CoA -> isopentenyl diphosphate); statin target, mevalonate kinase deficiency modules/mevalonate_pathway.yaml R-HSA-191352 activity_evidence hmgcr_step (S)-HMG-CoA + 2 NADPH to (R)-mevalonate + CoA REACTION hmgcr_activity HMGCR: HMG-CoA reductase GO:0004420 hydroxymethylglutaryl-CoA reductase (NADPH) activity UniProtKB:P04035 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMGCR dimer reduces bHMG-CoA to MVA (human Reactome reaction) yes reactome/R-HSA-191352.md HMGCR dimer reduces bHMG-CoA to MVA Homo sapiens mevalonate_pathway Mevalonate pathway (acetyl-CoA -> isopentenyl diphosphate); statin target, mevalonate kinase deficiency modules/mevalonate_pathway.yaml R-HSA-191380 activity_evidence mvk_step (R)-mevalonate + ATP to (R)-mevalonate-5-phosphate + ADP REACTION mvk_activity MVK: mevalonate kinase GO:0004496 mevalonate kinase activity UniProtKB:Q03426 Mevalonate kinase Mevalonate is phosphorylated to mevalonate-5-phosphate (human Reactome reaction) yes reactome/R-HSA-191380.md Mevalonate is phosphorylated to mevalonate-5-phosphate Homo sapiens mevalonate_pathway Mevalonate pathway (acetyl-CoA -> isopentenyl diphosphate); statin target, mevalonate kinase deficiency modules/mevalonate_pathway.yaml R-HSA-191414 activity_evidence mvd_step (R)-mevalonate-5-diphosphate + ATP to isopentenyl diphosphate + CO2 + ADP + Pi REACTION mvd_activity MVD: diphosphomevalonate decarboxylase GO:0004163 diphosphomevalonate decarboxylase activity UniProtKB:P53602 Diphosphomevalonate decarboxylase MVD decarboxylates MVA5PP to IPPP (human Reactome reaction) yes reactome/R-HSA-191414.md MVD decarboxylates MVA5PP to IPPP Homo sapiens mevalonate_pathway Mevalonate pathway (acetyl-CoA -> isopentenyl diphosphate); statin target, mevalonate kinase deficiency modules/mevalonate_pathway.yaml R-HSA-191422 activity_evidence pmvk_step (R)-mevalonate-5-phosphate + ATP to (R)-mevalonate-5-diphosphate + ADP REACTION pmvk_activity PMVK: phosphomevalonate kinase GO:0004631 phosphomevalonate kinase activity UniProtKB:Q15126 Phosphomevalonate kinase Mevalonate-5-phosphate is further phosphorylated (human Reactome reaction) yes reactome/R-HSA-191422.md Mevalonate-5-phosphate is further phosphorylated Homo sapiens mitochondrial_complex_i_core Mitochondrial respiratory Complex I core (NADH:ubiquinone oxidoreductase) — catalytic N and Q modules; NDUFV1/NDUFV2/NDUFS1-3/NDUFS6-8/NDUFA9 modules/mitochondrial_complex_i_core.yaml R-HSA-163217 module_evidence "The catalytic reaction follows the human Reactome ""Complex I oxidises NADH to NAD+, reduces CoQ to CoQH2"" reaction (R-HSA-163217)." yes reactome/R-HSA-163217.md Complex I oxidises NADH to NAD+, reduces CoQ to CoQH2 Homo sapiens mitochondrial_complex_i_core Mitochondrial respiratory Complex I core (NADH:ubiquinone oxidoreductase) — catalytic N and Q modules; NDUFV1/NDUFV2/NDUFS1-3/NDUFS6-8/NDUFA9 modules/mitochondrial_complex_i_core.yaml R-HSA-163217 activity_evidence complex_i_n_module N-module (flavoprotein / NADH-oxidising) PROTEIN_COMPLEX ndufv1_activity NDUFV1: FMN/NADH catalytic subunit (51 kDa) GO:0003954 NADH dehydrogenase activity UniProtKB:P49821 NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial Complex I oxidises NADH to NAD+, reduces CoQ to CoQH2 (human Reactome reaction) yes reactome/R-HSA-163217.md Complex I oxidises NADH to NAD+, reduces CoQ to CoQH2 Homo sapiens mitochondrial_complex_ii Mitochondrial respiratory Complex II (succinate dehydrogenase) + assembly factors; SDHA/SDHB/SDHC/SDHD + SDHAF1/SDHAF2 modules/mitochondrial_complex_ii.yaml R-HSA-70994 module_evidence "The catalytic reaction follows the human Reactome ""SDH complex dehydrogenates succinate"" reaction (R-HSA-70994)." yes reactome/R-HSA-70994.md SDH complex dehydrogenates succinate Homo sapiens mitochondrial_complex_ii Mitochondrial respiratory Complex II (succinate dehydrogenase) + assembly factors; SDHA/SDHB/SDHC/SDHD + SDHAF1/SDHAF2 modules/mitochondrial_complex_ii.yaml R-HSA-70994 activity_evidence sdh_holoenzyme Succinate dehydrogenase holoenzyme (SDHA/SDHB/SDHC/SDHD) PROTEIN_COMPLEX sdha_activity SDHA: FAD flavoprotein / succinate-oxidising subunit GO:0000104 succinate dehydrogenase activity UniProtKB:P31040 Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial SDH complex dehydrogenates succinate to fumarate (human Reactome reaction) yes reactome/R-HSA-70994.md SDH complex dehydrogenates succinate Homo sapiens mitochondrial_complex_iii Mitochondrial respiratory Complex III (cytochrome bc1) — subunits and assembly; UQCRC1/UQCRC2/UQCRB/UQCRQ/UQCRH/UQCRFS1/CYC1 + BCS1L/LYRM7/TTC19/UQCC2/UQCC3 modules/mitochondrial_complex_iii.yaml R-HSA-164651 activity_evidence complex_iii_holo Complex III (cytochrome bc1) electron transfer PROTEIN_COMPLEX cyc1_activity CYC1: cytochrome c1 GO:0009055 electron transfer activity UniProtKB:P08574 Cytochrome c1, heme protein, mitochondrial Electron transfer from ubiquinol to cytochrome c of complex III (human Reactome reaction) yes reactome/R-HSA-164651.md Electron transfer from ubiquinol to cytochrome c of complex III Homo sapiens mitochondrial_complex_iii Mitochondrial respiratory Complex III (cytochrome bc1) — subunits and assembly; UQCRC1/UQCRC2/UQCRB/UQCRQ/UQCRH/UQCRFS1/CYC1 + BCS1L/LYRM7/TTC19/UQCC2/UQCC3 modules/mitochondrial_complex_iii.yaml R-HSA-164651 activity_evidence complex_iii_holo Complex III (cytochrome bc1) electron transfer PROTEIN_COMPLEX uqcrfs1_activity UQCRFS1: Rieske [2Fe-2S] iron-sulfur protein GO:0009055 electron transfer activity UniProtKB:P47985 Cytochrome b-c1 complex subunit Rieske, mitochondrial Electron transfer from ubiquinol to cytochrome c of complex III (human Reactome reaction) yes reactome/R-HSA-164651.md Electron transfer from ubiquinol to cytochrome c of complex III Homo sapiens mitochondrial_complex_iii Mitochondrial respiratory Complex III (cytochrome bc1) — subunits and assembly; UQCRC1/UQCRC2/UQCRB/UQCRQ/UQCRH/UQCRFS1/CYC1 + BCS1L/LYRM7/TTC19/UQCC2/UQCC3 modules/mitochondrial_complex_iii.yaml R-HSA-9865881 module_evidence "The subunit incorporation and Rieske-maturation steps follow the human Reactome ""Complex III assembly"" pathway (reactions R-HSA-9866253/9866272 LYRM7/Rieske, R-HSA-9906042 TTC19)." yes reactome/R-HSA-9865881.md Complex III assembly Homo sapiens mitochondrial_complex_iii Mitochondrial respiratory Complex III (cytochrome bc1) — subunits and assembly; UQCRC1/UQCRC2/UQCRB/UQCRQ/UQCRH/UQCRFS1/CYC1 + BCS1L/LYRM7/TTC19/UQCC2/UQCC3 modules/mitochondrial_complex_iii.yaml R-HSA-9865881 node_evidence complex_iii_assembly Complex III assembly and Rieske Fe-S maturation REACTION Complex III assembly (human Reactome pathway) yes reactome/R-HSA-9865881.md Complex III assembly Homo sapiens mitochondrial_complex_iii Mitochondrial respiratory Complex III (cytochrome bc1) — subunits and assembly; UQCRC1/UQCRC2/UQCRB/UQCRQ/UQCRH/UQCRFS1/CYC1 + BCS1L/LYRM7/TTC19/UQCC2/UQCC3 modules/mitochondrial_complex_iii.yaml R-HSA-9866253 activity_evidence complex_iii_assembly Complex III assembly and Rieske Fe-S maturation REACTION lyrm7_activity LYRM7: Rieske (UQCRFS1) matrix chaperone GO:0044183 protein folding chaperone UniProtKB:Q5U5X0 Complex III assembly factor LYRM7 apo-UQCRFS1 binds LYRM7 (human Reactome reaction) yes reactome/R-HSA-9866253.md apo-UQCRFS1 binds LYRM7 Homo sapiens mitochondrial_complex_iii Mitochondrial respiratory Complex III (cytochrome bc1) — subunits and assembly; UQCRC1/UQCRC2/UQCRB/UQCRQ/UQCRH/UQCRFS1/CYC1 + BCS1L/LYRM7/TTC19/UQCC2/UQCC3 modules/mitochondrial_complex_iii.yaml R-HSA-9866272 activity_evidence complex_iii_assembly Complex III assembly and Rieske Fe-S maturation REACTION bcs1l_activity BCS1L: Rieske-insertion AAA-ATPase translocase GO:0008320 protein transmembrane transporter activity UniProtKB:Q9Y276 Mitochondrial chaperone BCS1 2Fe-2S is inserted in UQCRFS1 (human Reactome reaction) yes reactome/R-HSA-9866272.md 2Fe-2S is inserted in UQCRFS1 Homo sapiens mitochondrial_complex_iii Mitochondrial respiratory Complex III (cytochrome bc1) — subunits and assembly; UQCRC1/UQCRC2/UQCRB/UQCRQ/UQCRH/UQCRFS1/CYC1 + BCS1L/LYRM7/TTC19/UQCC2/UQCC3 modules/mitochondrial_complex_iii.yaml R-HSA-9906042 node_evidence complex_iii_assembly Complex III assembly and Rieske Fe-S maturation REACTION TTC19 clears UQCRFS1 fragments from Complex III (human Reactome reaction) yes reactome/R-HSA-9906042.md TTC19 clears UQCRFS1 fragments from Complex III Homo sapiens mitochondrial_complex_iv Mitochondrial respiratory Complex IV (cytochrome c oxidase) — nuclear subunits and MT-CO1/CO2 assembly; COX5A/COX6A2/COX7B/COX8A + COX14/COX20 modules/mitochondrial_complex_iv.yaml R-HSA-163214 module_evidence The catalytic reaction and the ordered subunit/MT-CO1/MT-CO2 assembly follow the human Reactome cytochrome-c-oxidase reactions R-HSA-163214, R-HSA-9865412 and R-HSA-9902096. yes reactome/R-HSA-163214.md Electron transfer from reduced cytochrome c to molecular oxygen Homo sapiens mitochondrial_complex_iv Mitochondrial respiratory Complex IV (cytochrome c oxidase) — nuclear subunits and MT-CO1/CO2 assembly; COX5A/COX6A2/COX7B/COX8A + COX14/COX20 modules/mitochondrial_complex_iv.yaml R-HSA-9865412 node_evidence complex_iv_assembly Complex IV assembly (MT-CO1/MT-CO2 maturation) REACTION TIMM21 carries COX4, COX5A, COX6C to MT-CO1:MITRAC (human Reactome reaction) yes reactome/R-HSA-9865412.md TIMM21 carries COX4, COX5A, COX6C to MT-CO1:MITRAC Homo sapiens mitochondrial_complex_iv Mitochondrial respiratory Complex IV (cytochrome c oxidase) — nuclear subunits and MT-CO1/CO2 assembly; COX5A/COX6A2/COX7B/COX8A + COX14/COX20 modules/mitochondrial_complex_iv.yaml R-HSA-9902096 node_evidence complex_iv_assembly Complex IV assembly (MT-CO1/MT-CO2 maturation) REACTION COX18 inserts nascent MT-CO2 in COX20:TMEM77 (human Reactome reaction) yes reactome/R-HSA-9902096.md COX18 inserts nascent MT-CO2 in COX20:TMEM77 Homo sapiens mitochondrial_complex_v Mitochondrial respiratory Complex V (F1Fo ATP synthase) — subunits and F1 assembly; ATP5F1A/ATP5F1B/ATP5F1D/ATP5F1E/ATP5PO/ATP5MC3/ATP5MD + ATPAF2/TMEM70 modules/mitochondrial_complex_v.yaml R-HSA-164832 activity_evidence complex_v_f1 F1 sector (alpha3-beta3 catalytic head + central stalk) PROTEIN_COMPLEX atp5f1a_activity ATP5F1A: F1 alpha subunit GO:0046933 proton-transporting ATP synthase activity, rotational mechanism UniProtKB:P25705 ATP synthase subunit alpha, mitochondrial ATPase synthesizes ATP (human Reactome reaction) yes reactome/R-HSA-164832.md ATPase synthesizes ATP Homo sapiens mitochondrial_complex_v Mitochondrial respiratory Complex V (F1Fo ATP synthase) — subunits and F1 assembly; ATP5F1A/ATP5F1B/ATP5F1D/ATP5F1E/ATP5PO/ATP5MC3/ATP5MD + ATPAF2/TMEM70 modules/mitochondrial_complex_v.yaml R-HSA-164832 activity_evidence complex_v_f1 F1 sector (alpha3-beta3 catalytic head + central stalk) PROTEIN_COMPLEX atp5f1b_activity ATP5F1B: F1 beta subunit (catalytic) GO:0046933 proton-transporting ATP synthase activity, rotational mechanism UniProtKB:P06576 ATP synthase subunit beta, mitochondrial ATPase synthesizes ATP (human Reactome reaction) yes reactome/R-HSA-164832.md ATPase synthesizes ATP Homo sapiens mitochondrial_complex_v Mitochondrial respiratory Complex V (F1Fo ATP synthase) — subunits and F1 assembly; ATP5F1A/ATP5F1B/ATP5F1D/ATP5F1E/ATP5PO/ATP5MC3/ATP5MD + ATPAF2/TMEM70 modules/mitochondrial_complex_v.yaml R-HSA-8949580 module_evidence The catalytic cycle and assembly follow the human Reactome ATP-synthase reactions R-HSA-164832 (ATP synthesis) and R-HSA-8949580 (F1Fo dimerisation). yes reactome/R-HSA-8949580.md F1Fo ATP synthase dimerizes Homo sapiens mitochondrial_complex_v Mitochondrial respiratory Complex V (F1Fo ATP synthase) — subunits and F1 assembly; ATP5F1A/ATP5F1B/ATP5F1D/ATP5F1E/ATP5PO/ATP5MC3/ATP5MD + ATPAF2/TMEM70 modules/mitochondrial_complex_v.yaml R-HSA-8949580 node_evidence complex_v_assembly ATP synthase assembly (F1 chaperone and dimerisation) REACTION F1Fo ATP synthase dimerizes (human Reactome reaction) yes reactome/R-HSA-8949580.md F1Fo ATP synthase dimerizes Homo sapiens mitochondrial_dntp_supply Mitochondrial dNTP supply for mtDNA maintenance — MNGIE and mtDNA depletion syndromes modules/mitochondrial_dntp_supply.yaml R-HSA-109759 activity_evidence tk2_step thymidine / deoxycytidine / deoxyuridine + ATP to dTMP / dCMP / dUMP REACTION tk2_activity TK2: mitochondrial thymidine kinase 2 GO:0004797 thymidine kinase activity UniProtKB:O00142 Thymidine kinase 2, mitochondrial deoxycytidine, thymidine, or deoxyuridine + ATP => dCMP, TMP, or dUMP (human Reactome reaction) yes reactome/R-HSA-109759.md deoxycytidine, thymidine, or deoxyuridine + ATP => dCMP, TMP, or dUMP + ADP [TK2] Homo sapiens mitochondrial_dntp_supply Mitochondrial dNTP supply for mtDNA maintenance — MNGIE and mtDNA depletion syndromes modules/mitochondrial_dntp_supply.yaml R-HSA-111804 activity_evidence rrm2b_step ribonucleoside diphosphate (NDP) to 2'-deoxyribonucleoside diphosphate (dNDP) REACTION rrm2b_activity RRM2B (p53R2): ribonucleotide reductase small subunit GO:0004748 ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor UniProtKB:Q7LG56 Ribonucleoside-diphosphate reductase subunit M2 B RNR (M1M2B) reduces nucleotide diphosphates to deoxynucleotide diphosphates (human Reactome reaction) yes reactome/R-HSA-111804.md RNR (M1M2B) reduces nucleotide diphosphates to deoxynucleotide diphosphates (thioredoxin) Homo sapiens mitochondrial_dntp_supply Mitochondrial dNTP supply for mtDNA maintenance — MNGIE and mtDNA depletion syndromes modules/mitochondrial_dntp_supply.yaml R-HSA-112265 activity_evidence tymp_step thymidine + phosphate <-> thymine + 2-deoxyribose-1-phosphate REACTION tymp_activity TYMP: thymidine phosphorylase GO:0009032 thymidine phosphorylase activity UniProtKB:P19971 Thymidine phosphorylase thymidine or deoxyuridine + orthophosphate <=> thymine or uracil + 2-deoxy-D-ribose 1-phosphate (human Reactome reaction) yes reactome/R-HSA-112265.md thymidine or deoxyuridine + orthophosphate <=> thymine or uracil + 2-deoxy-D-ribose 1-phosphate [TYMP] Homo sapiens mitochondrial_dntp_supply Mitochondrial dNTP supply for mtDNA maintenance — MNGIE and mtDNA depletion syndromes modules/mitochondrial_dntp_supply.yaml R-HSA-74207 activity_evidence dguok_step deoxyguanosine / deoxyadenosine + ATP to dGMP / dAMP REACTION dguok_activity DGUOK: mitochondrial deoxyguanosine kinase GO:0004138 deoxyguanosine kinase activity UniProtKB:Q16854 Deoxyguanosine kinase, mitochondrial dA, dG, or dI + ATP => dAMP, dGMP, or dIMP + ADP (DGUOK) (human Reactome reaction) yes reactome/R-HSA-74207.md dA, dG, or dI + ATP => dAMP, dGMP, or dIMP + ADP (DGUOK) Homo sapiens n_glycan_llo_assembly_cytoplasmic N-glycan LLO assembly I — cytoplasmic face (to Man5GlcNAc2-PP-dolichol); DPAGT1/ALG13/ALG14/ALG1/ALG2/ALG11 modules/n_glycan_llo_assembly_cytoplasmic.yaml R-HSA-446191 activity_evidence dpagt1_step UDP-GlcNAc + dolichyl phosphate to GlcNAc-PP-dolichol REACTION dpagt1_activity DPAGT1: GlcNAc-1-phosphotransferase GO:0003975 UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase activity UniProtKB:Q9H3H5 UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase Addition of N-acetyl-D-glucosamine to Dolichyl phosphate (human Reactome reaction) yes reactome/R-HSA-446191.md Addition of N-acetyl-D-glucosamine to Dolichyl phosphate Homo sapiens n_glycan_llo_assembly_cytoplasmic N-glycan LLO assembly I — cytoplasmic face (to Man5GlcNAc2-PP-dolichol); DPAGT1/ALG13/ALG14/ALG1/ALG2/ALG11 modules/n_glycan_llo_assembly_cytoplasmic.yaml R-HSA-446193 module_evidence Step order, intermediates and reaction stoichiometries follow the human Reactome LLO biosynthesis sub-pathway (R-HSA-446191/446207/446218/446208 for the cytoplasmic-face steps). yes reactome/R-HSA-446193.md Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein Homo sapiens n_glycan_llo_assembly_cytoplasmic N-glycan LLO assembly I — cytoplasmic face (to Man5GlcNAc2-PP-dolichol); DPAGT1/ALG13/ALG14/ALG1/ALG2/ALG11 modules/n_glycan_llo_assembly_cytoplasmic.yaml R-HSA-446193 activity_evidence alg11_step Man3GlcNAc2-PP-dolichol to Man5GlcNAc2-PP-dolichol REACTION alg11_activity ALG11: alpha-1,2-mannosyltransferase GO:0004377 GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity UniProtKB:Q2TAA5 GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein (human Reactome pathway) yes reactome/R-HSA-446193.md Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein Homo sapiens n_glycan_llo_assembly_cytoplasmic N-glycan LLO assembly I — cytoplasmic face (to Man5GlcNAc2-PP-dolichol); DPAGT1/ALG13/ALG14/ALG1/ALG2/ALG11 modules/n_glycan_llo_assembly_cytoplasmic.yaml R-HSA-446207 activity_evidence alg13_14_step GlcNAc-PP-dolichol to GlcNAc2-PP-dolichol PROTEIN_COMPLEX alg13_activity ALG13: catalytic subunit of the UDP-GlcNAc transferase GO:0004577 N-acetylglucosaminyldiphosphodolichol N-acetylglucosaminyltransferase activity UniProtKB:Q9NP73 UDP-N-acetylglucosamine transferase subunit ALG13 homolog ALG13:ALG14 transfers GlcNAc from UDP-GlcNAc to GlcNAcDOLP (human Reactome reaction) yes reactome/R-HSA-446207.md ALG13:ALG14 transfers GlcNAc from UDP-GlcNAc to GlcNAcDOLP Homo sapiens n_glycan_llo_assembly_cytoplasmic N-glycan LLO assembly I — cytoplasmic face (to Man5GlcNAc2-PP-dolichol); DPAGT1/ALG13/ALG14/ALG1/ALG2/ALG11 modules/n_glycan_llo_assembly_cytoplasmic.yaml R-HSA-446207 activity_evidence alg13_14_step GlcNAc-PP-dolichol to GlcNAc2-PP-dolichol PROTEIN_COMPLEX alg14_activity ALG14: membrane-anchoring subunit GO:0043495 protein-membrane adaptor activity UniProtKB:Q96F25 UDP-N-acetylglucosamine transferase subunit ALG14 homolog ALG13:ALG14 transfers GlcNAc from UDP-GlcNAc to GlcNAcDOLP (human Reactome reaction) yes reactome/R-HSA-446207.md ALG13:ALG14 transfers GlcNAc from UDP-GlcNAc to GlcNAcDOLP Homo sapiens n_glycan_llo_assembly_cytoplasmic N-glycan LLO assembly I — cytoplasmic face (to Man5GlcNAc2-PP-dolichol); DPAGT1/ALG13/ALG14/ALG1/ALG2/ALG11 modules/n_glycan_llo_assembly_cytoplasmic.yaml R-HSA-446208 activity_evidence alg2_step Man1GlcNAc2-PP-dolichol to Man3GlcNAc2-PP-dolichol REACTION alg2_activity ALG2: alpha-1,3/1,6-mannosyltransferase GO:0004378 GDP-Man:Man(1)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activity UniProtKB:Q9H553 Alpha-1,3/1,6-mannosyltransferase ALG2 Addition of a second mannose to the N-glycan precursor by ALG2 (human Reactome reaction) yes reactome/R-HSA-446208.md Addition of a second mannose to the N-glycan precursor by ALG2 Homo sapiens n_glycan_llo_assembly_cytoplasmic N-glycan LLO assembly I — cytoplasmic face (to Man5GlcNAc2-PP-dolichol); DPAGT1/ALG13/ALG14/ALG1/ALG2/ALG11 modules/n_glycan_llo_assembly_cytoplasmic.yaml R-HSA-446218 activity_evidence alg1_step GlcNAc2-PP-dolichol to Man1GlcNAc2-PP-dolichol REACTION alg1_activity ALG1: beta-1,4-mannosyltransferase GO:0004578 chitobiosyldiphosphodolichol beta-mannosyltransferase activity UniProtKB:Q9BT22 Chitobiosyldiphosphodolichol beta-mannosyltransferase Addition of the first mannose to the N-glycan precursor by ALG1 (human Reactome reaction) yes reactome/R-HSA-446218.md Addition of the first mannose to the N-glycan precursor by ALG1 Homo sapiens n_glycan_llo_assembly_lumenal N-glycan LLO assembly II — ER-lumenal face + glucosylation (to Glc3Man9GlcNAc2-PP-dolichol); ALG3/ALG9/ALG12/ALG6/ALG8/ALG10 modules/n_glycan_llo_assembly_lumenal.yaml R-HSA-446188 activity_evidence alg3_step Man5GlcNAc2-PP-dolichol to Man6GlcNAc2-PP-dolichol REACTION alg3_activity ALG3: Dol-P-Man alpha-1,3-mannosyltransferase GO:0052925 dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activity UniProtKB:Q92685 Dol-P-Man:Man(5)GlcNAc(2)-PP-dolichol alpha-1,3-mannosyltransferase ALG3 transfers Man to N-glycan precursor (GlcNAc)2 (Man)5 (PP-Dol) (human Reactome reaction) yes reactome/R-HSA-446188.md ALG3 transfers Man to N-glycan precursor (GlcNAc)2 (Man)5 (PP-Dol)1 Homo sapiens n_glycan_llo_assembly_lumenal N-glycan LLO assembly II — ER-lumenal face + glucosylation (to Glc3Man9GlcNAc2-PP-dolichol); ALG3/ALG9/ALG12/ALG6/ALG8/ALG10 modules/n_glycan_llo_assembly_lumenal.yaml R-HSA-446189 activity_evidence alg8_step Glc1Man9GlcNAc2-PP-dolichol to Glc2Man9GlcNAc2-PP-dolichol REACTION alg8_activity ALG8: Dol-P-Glc alpha-1,3-glucosyltransferase GO:0042283 dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity UniProtKB:Q9BVK2 Dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase Addition of a second glucose to the N-glycan precursor by ALG8 (human Reactome reaction) yes reactome/R-HSA-446189.md Addition of a second glucose to the N-glycan precursor by ALG8 Homo sapiens n_glycan_llo_assembly_lumenal N-glycan LLO assembly II — ER-lumenal face + glucosylation (to Glc3Man9GlcNAc2-PP-dolichol); ALG3/ALG9/ALG12/ALG6/ALG8/ALG10 modules/n_glycan_llo_assembly_lumenal.yaml R-HSA-446193 module_evidence Step order, intermediates and reaction stoichiometries follow the human Reactome LLO biosynthesis sub-pathway (R-HSA-446188/446215/446198/446216/446202/446189 for the lumenal steps). yes reactome/R-HSA-446193.md Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein Homo sapiens n_glycan_llo_assembly_lumenal N-glycan LLO assembly II — ER-lumenal face + glucosylation (to Glc3Man9GlcNAc2-PP-dolichol); ALG3/ALG9/ALG12/ALG6/ALG8/ALG10 modules/n_glycan_llo_assembly_lumenal.yaml R-HSA-446193 activity_evidence alg10_step Glc2Man9GlcNAc2-PP-dolichol to Glc3Man9GlcNAc2-PP-dolichol (mature LLO) REACTION alg10_activity ALG10: Dol-P-Glc alpha-1,2-glucosyltransferase GO:0106073 dolichyl pyrophosphate Glc2Man9GlcNAc2 alpha-1,2-glucosyltransferase activity UniProtKB:Q5BKT4 Putative dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-dolichol alpha-1,2-glucosyltransferase Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein (human Reactome pathway) yes reactome/R-HSA-446193.md Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein Homo sapiens n_glycan_llo_assembly_lumenal N-glycan LLO assembly II — ER-lumenal face + glucosylation (to Glc3Man9GlcNAc2-PP-dolichol); ALG3/ALG9/ALG12/ALG6/ALG8/ALG10 modules/n_glycan_llo_assembly_lumenal.yaml R-HSA-446198 activity_evidence alg12_step Man7GlcNAc2-PP-dolichol to Man8GlcNAc2-PP-dolichol REACTION alg12_activity ALG12: Dol-P-Man alpha-1,6-mannosyltransferase GO:0052917 dol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase activity UniProtKB:Q9BV10 Dol-P-Man:Man(7)GlcNAc(2)-PP-dolichol alpha-1,6-mannosyltransferase ALG12 transfers Man to N-glycan precursor (GlcNAc)2 (Man)7 (PP-Dol) (human Reactome reaction) yes reactome/R-HSA-446198.md ALG12 transfers Man to N-glycan precursor (GlcNAc)2 (Man)7 (PP-Dol)1 Homo sapiens n_glycan_llo_assembly_lumenal N-glycan LLO assembly II — ER-lumenal face + glucosylation (to Glc3Man9GlcNAc2-PP-dolichol); ALG3/ALG9/ALG12/ALG6/ALG8/ALG10 modules/n_glycan_llo_assembly_lumenal.yaml R-HSA-446202 activity_evidence alg6_step Man9GlcNAc2-PP-dolichol to Glc1Man9GlcNAc2-PP-dolichol REACTION alg6_activity ALG6: Dol-P-Glc alpha-1,3-glucosyltransferase GO:0042281 dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase activity UniProtKB:Q9Y672 Dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase Addition of the first glucose to the N-glycan precursor by ALG6 (human Reactome reaction) yes reactome/R-HSA-446202.md Addition of the first glucose to the N-glycan precursor by ALG6 Homo sapiens n_glycan_llo_assembly_lumenal N-glycan LLO assembly II — ER-lumenal face + glucosylation (to Glc3Man9GlcNAc2-PP-dolichol); ALG3/ALG9/ALG12/ALG6/ALG8/ALG10 modules/n_glycan_llo_assembly_lumenal.yaml R-HSA-446215 activity_evidence alg9_step7 Man6GlcNAc2-PP-dolichol to Man7GlcNAc2-PP-dolichol REACTION alg9_activity_m7 ALG9: Dol-P-Man alpha-1,2-mannosyltransferase (7th Man) GO:0052926 dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity UniProtKB:Q9H6U8 Alpha-1,2-mannosyltransferase ALG9 ALG9 transfers Man to N-glycan precursor (GlcNAc)2 (Man)6 (PP-Dol) (human Reactome reaction) yes reactome/R-HSA-446215.md ALG9 transfers Man to N-glycan precursor (GlcNAc)2 (Man)6 (PP-Dol)1 Homo sapiens n_glycan_llo_assembly_lumenal N-glycan LLO assembly II — ER-lumenal face + glucosylation (to Glc3Man9GlcNAc2-PP-dolichol); ALG3/ALG9/ALG12/ALG6/ALG8/ALG10 modules/n_glycan_llo_assembly_lumenal.yaml R-HSA-446216 activity_evidence alg9_step9 Man8GlcNAc2-PP-dolichol to Man9GlcNAc2-PP-dolichol REACTION alg9_activity_m9 ALG9: Dol-P-Man alpha-1,2-mannosyltransferase (9th Man) GO:0052918 dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity UniProtKB:Q9H6U8 Alpha-1,2-mannosyltransferase ALG9 ALG9 transfers Man to N-glycan precursor (GlcNAc)2 (Man)8 (PP-Dol) (human Reactome reaction) yes reactome/R-HSA-446216.md ALG9 transfers Man to N-glycan precursor (GlcNAc)2 (Man)8 (PP-Dol)1 Homo sapiens pentose_phosphate_nonoxidative_branch Pentose phosphate pathway — non-oxidative branch + PRPP synthesis; transaldolase/RPIA deficiency, PRPS1 disorders modules/pentose_phosphate_nonoxidative_branch.yaml R-HSA-177784 activity_evidence rpia_step D-ribulose-5-phosphate to D-ribose-5-phosphate REACTION rpia_activity RPIA: ribose-5-phosphate isomerase GO:0004751 ribose-5-phosphate isomerase activity UniProtKB:P49247 Ribose-5-phosphate isomerase RPIA isomerizes ribose 5-phosphate to D-ribulose 5-phosphate (human Reactome reaction) yes reactome/R-HSA-177784.md RPIA isomerizes ribose 5-phosphate to D-ribulose 5-phosphate Homo sapiens pentose_phosphate_nonoxidative_branch Pentose phosphate pathway — non-oxidative branch + PRPP synthesis; transaldolase/RPIA deficiency, PRPS1 disorders modules/pentose_phosphate_nonoxidative_branch.yaml R-HSA-71303 activity_evidence rpe_step D-ribulose-5-phosphate to D-xylulose-5-phosphate REACTION rpe_activity RPE: ribulose-5-phosphate 3-epimerase GO:0004750 D-ribulose-phosphate 3-epimerase activity UniProtKB:Q96AT9 Ribulose-phosphate 3-epimerase RPE dimers isomerise RU5P to XY5P (human Reactome reaction) yes reactome/R-HSA-71303.md RPE dimers isomerise RU5P to XY5P Homo sapiens pentose_phosphate_nonoxidative_branch Pentose phosphate pathway — non-oxidative branch + PRPP synthesis; transaldolase/RPIA deficiency, PRPS1 disorders modules/pentose_phosphate_nonoxidative_branch.yaml R-HSA-71324 activity_evidence tkt_step D-xylulose-5-P + D-ribose-5-P to sedoheptulose-7-P + D-glyceraldehyde-3-P REACTION tkt_activity TKT: transketolase GO:0004802 transketolase activity UniProtKB:P29401 Transketolase ribose 5-phosphate + xylulose 5-phosphate <=> sedoheptulose 7-phosphate (human Reactome reaction) yes reactome/R-HSA-71324.md ribose 5-phosphate + xylulose 5-phosphate <=> sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate Homo sapiens pentose_phosphate_nonoxidative_branch Pentose phosphate pathway — non-oxidative branch + PRPP synthesis; transaldolase/RPIA deficiency, PRPS1 disorders modules/pentose_phosphate_nonoxidative_branch.yaml R-HSA-71334 activity_evidence taldo1_step sedoheptulose-7-P + D-glyceraldehyde-3-P to D-erythrose-4-P + D-fructose-6-P REACTION taldo1_activity TALDO1: transaldolase GO:0004801 transaldolase activity UniProtKB:P37837 Transaldolase sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate <=> D-erythrose 4-phosphate + D-fructose 6-phosphate (human Reactome reaction) yes reactome/R-HSA-71334.md sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate <=> D-erythrose 4-phosphate + D-fructose 6-phosphate Homo sapiens pentose_phosphate_nonoxidative_branch Pentose phosphate pathway — non-oxidative branch + PRPP synthesis; transaldolase/RPIA deficiency, PRPS1 disorders modules/pentose_phosphate_nonoxidative_branch.yaml R-HSA-71336 module_evidence "Reactions follow the human Reactome ""Pentose phosphate pathway"" (R-HSA-71336): R-HSA-177784 (RPIA), R-HSA-71303 (RPE), R-HSA-71324 (TKT), R-HSA-71334 (TALDO1) and R-HSA-73580 (PRPS1)." yes reactome/R-HSA-71336.md Pentose phosphate pathway Homo sapiens pentose_phosphate_nonoxidative_branch Pentose phosphate pathway — non-oxidative branch + PRPP synthesis; transaldolase/RPIA deficiency, PRPS1 disorders modules/pentose_phosphate_nonoxidative_branch.yaml R-HSA-73580 activity_evidence prps1_step D-ribose-5-phosphate + ATP to PRPP + AMP REACTION prps1_activity PRPS1: phosphoribosyl pyrophosphate synthetase 1 GO:0004749 ribose phosphate diphosphokinase activity UniProtKB:P60891 Ribose-phosphate pyrophosphokinase 1 PRPS dimers pyrophosphorylate R5P using ATP (human Reactome reaction) yes reactome/R-HSA-73580.md PRPS dimers pyrophosphorylate R5P using ATP Homo sapiens pentose_phosphate_oxidative_branch Pentose phosphate pathway — oxidative branch (NADPH generation); G6PD deficiency / favism modules/pentose_phosphate_oxidative_branch.yaml R-HSA-70377 activity_evidence g6pd_step D-glucose-6-phosphate + NADP+ to 6-phospho-D-glucono-1,5-lactone + NADPH REACTION g6pd_activity G6PD: glucose-6-phosphate dehydrogenase GO:0004345 glucose-6-phosphate dehydrogenase activity UniProtKB:P11413 Glucose-6-phosphate 1-dehydrogenase G6PD multimers dehydrogenate G6P (human Reactome reaction) yes reactome/R-HSA-70377.md G6PD multimers dehydrogenate G6P Homo sapiens pentose_phosphate_oxidative_branch Pentose phosphate pathway — oxidative branch (NADPH generation); G6PD deficiency / favism modules/pentose_phosphate_oxidative_branch.yaml R-HSA-71296 activity_evidence pgls_step 6-phospho-D-glucono-1,5-lactone + H2O to 6-phospho-D-gluconate REACTION pgls_activity PGLS: 6-phosphogluconolactonase GO:0017057 6-phosphogluconolactonase activity UniProtKB:O95336 6-phosphogluconolactonase PGLS hydrolyzes D-glucono-1,5-lactone 6-phosphate (human Reactome reaction) yes reactome/R-HSA-71296.md PGLS hydrolyzes D-glucono-1,5-lactone 6-phosphate Homo sapiens pentose_phosphate_oxidative_branch Pentose phosphate pathway — oxidative branch (NADPH generation); G6PD deficiency / favism modules/pentose_phosphate_oxidative_branch.yaml R-HSA-71299 activity_evidence pgd_step 6-phospho-D-gluconate + NADP+ to D-ribulose-5-phosphate + CO2 + NADPH REACTION pgd_activity PGD: 6-phosphogluconate dehydrogenase (decarboxylating) GO:0004616 phosphogluconate dehydrogenase (decarboxylating) activity UniProtKB:P52209 6-phosphogluconate dehydrogenase, decarboxylating PGD decarboxylates 6-phospho-D-gluconate (human Reactome reaction) yes reactome/R-HSA-71299.md PGD decarboxylates 6-phospho-D-gluconate Homo sapiens pentose_phosphate_oxidative_branch Pentose phosphate pathway — oxidative branch (NADPH generation); G6PD deficiency / favism modules/pentose_phosphate_oxidative_branch.yaml R-HSA-71336 module_evidence "Step order and reaction stoichiometries follow the human Reactome ""Pentose phosphate pathway"" reactions R-HSA-70377 (G6PD), R-HSA-71296 (PGLS) and R-HSA-71299 (PGD)." yes reactome/R-HSA-71336.md Pentose phosphate pathway Homo sapiens phosphocreatine_shuttle Phosphocreatine shuttle / creatine kinase system (human) modules/phosphocreatine_shuttle.yaml R-HSA-200318 activity_evidence cyto_ck_step phosphocreatine + ADP to creatine + ATP (cytosolic) REACTION ck_bb_activity CK-BB: creatine kinase B-type homodimer GO:0004111 creatine kinase activity UniProtKB:P12277 Creatine kinase B-type creatine + ATP => phosphocreatine + ADP [CKB,CKM] (human Reactome reaction; cytosolic CK) yes reactome/R-HSA-200318.md creatine + ATP => phosphocreatine + ADP [CKB,CKM] Homo sapiens phosphocreatine_shuttle Phosphocreatine shuttle / creatine kinase system (human) modules/phosphocreatine_shuttle.yaml R-HSA-200318 activity_evidence cyto_ck_step phosphocreatine + ADP to creatine + ATP (cytosolic) REACTION ck_mb_activity CK-MB: creatine kinase M-type/B-type heterodimer GO:0004111 creatine kinase activity UniProtKB:P06732|UniProtKB:P12277 Creatine kinase M-type|Creatine kinase B-type creatine + ATP => phosphocreatine + ADP [CKB,CKM] (human Reactome reaction; cytosolic CK) yes reactome/R-HSA-200318.md creatine + ATP => phosphocreatine + ADP [CKB,CKM] Homo sapiens phosphocreatine_shuttle Phosphocreatine shuttle / creatine kinase system (human) modules/phosphocreatine_shuttle.yaml R-HSA-200318 activity_evidence cyto_ck_step phosphocreatine + ADP to creatine + ATP (cytosolic) REACTION ck_mm_activity CK-MM: creatine kinase M-type homodimer GO:0004111 creatine kinase activity UniProtKB:P06732 Creatine kinase M-type creatine + ATP => phosphocreatine + ADP [CKB,CKM] (human Reactome reaction; cytosolic CK) yes reactome/R-HSA-200318.md creatine + ATP => phosphocreatine + ADP [CKB,CKM] Homo sapiens phosphocreatine_shuttle Phosphocreatine shuttle / creatine kinase system (human) modules/phosphocreatine_shuttle.yaml R-HSA-200326 activity_evidence mito_ck_step ATP + creatine to ADP + phosphocreatine (mitochondrial) REACTION ckmt1_octamer_activity CK octamer (ubiquitous): CKMT1A homo-octamer GO:0004111 creatine kinase activity UniProtKB:P12532 Creatine kinase U-type, mitochondrial creatine + ATP => phosphocreatine + ADP [CK octamer] (human Reactome reaction; mitochondrial CK) yes reactome/R-HSA-200326.md creatine + ATP => phosphocreatine + ADP [CK octamer] Homo sapiens phosphocreatine_shuttle Phosphocreatine shuttle / creatine kinase system (human) modules/phosphocreatine_shuttle.yaml R-HSA-200326 activity_evidence mito_ck_step ATP + creatine to ADP + phosphocreatine (mitochondrial) REACTION ckmt2_octamer_activity CK octamer (sarcomeric): CKMT2 homo-octamer GO:0004111 creatine kinase activity UniProtKB:P17540 Creatine kinase S-type, mitochondrial creatine + ATP => phosphocreatine + ADP [CK octamer] (human Reactome reaction; mitochondrial CK) yes reactome/R-HSA-200326.md creatine + ATP => phosphocreatine + ADP [CK octamer] Homo sapiens phosphocreatine_shuttle Phosphocreatine shuttle / creatine kinase system (human) modules/phosphocreatine_shuttle.yaml R-HSA-200339 activity_evidence mito_ck_step ATP + creatine to ADP + phosphocreatine (mitochondrial) REACTION ckmt2_octamer_activity CK octamer (sarcomeric): CKMT2 homo-octamer GO:0004111 creatine kinase activity UniProtKB:P17540 Creatine kinase S-type, mitochondrial creatine kinase, sarcomeric, octamer [mitochondrial inner membrane] (Reactome complex) no phosphocreatine_shuttle Phosphocreatine shuttle / creatine kinase system (human) modules/phosphocreatine_shuttle.yaml R-HSA-200341 activity_evidence cyto_ck_step phosphocreatine + ADP to creatine + ATP (cytosolic) REACTION ck_bb_activity CK-BB: creatine kinase B-type homodimer GO:0004111 creatine kinase activity UniProtKB:P12277 Creatine kinase B-type creatine kinase BB dimer [cytosol] (Reactome complex) no phosphocreatine_shuttle Phosphocreatine shuttle / creatine kinase system (human) modules/phosphocreatine_shuttle.yaml R-HSA-200358 activity_evidence mito_ck_step ATP + creatine to ADP + phosphocreatine (mitochondrial) REACTION ckmt1_octamer_activity CK octamer (ubiquitous): CKMT1A homo-octamer GO:0004111 creatine kinase activity UniProtKB:P12532 Creatine kinase U-type, mitochondrial creatine kinase, ubiquitous, octamer [mitochondrial inner membrane] (Reactome complex) no phosphocreatine_shuttle Phosphocreatine shuttle / creatine kinase system (human) modules/phosphocreatine_shuttle.yaml R-HSA-200359 activity_evidence cyto_ck_step phosphocreatine + ADP to creatine + ATP (cytosolic) REACTION ck_mm_activity CK-MM: creatine kinase M-type homodimer GO:0004111 creatine kinase activity UniProtKB:P06732 Creatine kinase M-type creatine kinase MM dimer [cytosol] (Reactome complex) no phosphocreatine_shuttle Phosphocreatine shuttle / creatine kinase system (human) modules/phosphocreatine_shuttle.yaml R-HSA-200374 activity_evidence cyto_ck_step phosphocreatine + ADP to creatine + ATP (cytosolic) REACTION ck_mb_activity CK-MB: creatine kinase M-type/B-type heterodimer GO:0004111 creatine kinase activity UniProtKB:P06732|UniProtKB:P12277 Creatine kinase M-type|Creatine kinase B-type creatine kinase BM dimer [cytosol] (Reactome complex; CK-MB heterodimer) no phosphorylase_kinase_complex Phosphorylase kinase complex (activates glycogenolysis) — GSD IX modules/phosphorylase_kinase_complex.yaml R-HSA-71588 module_evidence The activated holoenzyme phosphorylates glycogen phosphorylase b to a in the human Reactome reactions R-HSA-71588 (liver PYGL) and R-HSA-71541 (muscle PYGM), the activation step upstream of the glycogenolysis module. yes reactome/R-HSA-71588.md glycogen phosphorylase (PYGL) dimer b + 2 ATP => glycogen phosphorylase (PYGL) dimer a + 2 ADP Homo sapiens phosphorylase_kinase_complex Phosphorylase kinase complex (activates glycogenolysis) — GSD IX modules/phosphorylase_kinase_complex.yaml R-HSA-71588 activity_evidence phk_holoenzyme phosphorylase kinase (alpha-beta-gamma-delta)4 complex PROTEIN_COMPLEX phk_gamma PHKG1/PHKG2: catalytic gamma subunit GO:0004689 phosphorylase kinase activity UniProtKB:P15735 Phosphorylase b kinase gamma catalytic chain, liver/testis isoform glycogen phosphorylase (PYGL) dimer b + 2 ATP => glycogen phosphorylase [a] (human Reactome reaction) yes reactome/R-HSA-71588.md glycogen phosphorylase (PYGL) dimer b + 2 ATP => glycogen phosphorylase (PYGL) dimer a + 2 ADP Homo sapiens propionyl_coa_catabolism Propionyl-CoA catabolism (propionate to succinyl-CoA via the methylmalonyl-CoA pathway) modules/propionyl_coa_catabolism.yaml R-HSA-3159253 activity_evidence adocbl_supply AdoCbl synthesis (MMAB) and MMAA-gated loading onto the mutase REGULATORY_STEP mmab_activity MMAB/cblB: ATP:cob(I)alamin adenosyltransferase GO:0008817 cob(I)alamin adenosyltransferase activity UniProtKB:Q96EY8 Cob(I)yrinic acid a,c-diamide adenosyltransferase, mitochondrial MMAB adenosylates cob(I)alamin (human Reactome reaction) no propionyl_coa_catabolism Propionyl-CoA catabolism (propionate to succinyl-CoA via the methylmalonyl-CoA pathway) modules/propionyl_coa_catabolism.yaml R-HSA-3159259 activity_evidence adocbl_supply AdoCbl synthesis (MMAB) and MMAA-gated loading onto the mutase REGULATORY_STEP mmaa_activity MMAA/cblA: G3E GTPase chaperone for the mutase GO:0003924 GTPase activity UniProtKB:Q8IVH4 Methylmalonic aciduria type A protein, mitochondrial MMAA:MUT binds AdoCbl (human Reactome reaction) — GTP-dependent cofactor loading no propionyl_coa_catabolism Propionyl-CoA catabolism (propionate to succinyl-CoA via the methylmalonyl-CoA pathway) modules/propionyl_coa_catabolism.yaml R-HSA-71010 activity_evidence mmut_step (R)-methylmalonyl-CoA to succinyl-CoA REACTION mmut_activity MMUT: methylmalonyl-CoA mutase (AdoCbl-dependent) GO:0004494 methylmalonyl-CoA mutase activity UniProtKB:P22033 Methylmalonyl-CoA mutase, mitochondrial MUT isomerises L-MM-CoA to SUCC-CoA (human Reactome reaction) no propionyl_coa_catabolism Propionyl-CoA catabolism (propionate to succinyl-CoA via the methylmalonyl-CoA pathway) modules/propionyl_coa_catabolism.yaml R-HSA-71020 activity_evidence mcee_step (S)-methylmalonyl-CoA to (R)-methylmalonyl-CoA REACTION mcee_activity MCEE: methylmalonyl-CoA epimerase GO:0004493 methylmalonyl-CoA epimerase activity UniProtKB:Q96PE7 Methylmalonyl-CoA epimerase, mitochondrial D-methylmalonyl-CoA <=> L-methylmalonyl-CoA (human Reactome reaction) no propionyl_coa_catabolism Propionyl-CoA catabolism (propionate to succinyl-CoA via the methylmalonyl-CoA pathway) modules/propionyl_coa_catabolism.yaml R-HSA-71031 activity_evidence pcc_step propionyl-CoA + HCO3- + ATP to (S)-methylmalonyl-CoA + ADP + Pi PROTEIN_COMPLEX pcca_activity PCCA: propionyl-CoA carboxylase alpha (biotin carboxylase) GO:0004658 propionyl-CoA carboxylase activity UniProtKB:P05165 Propionyl-CoA carboxylase alpha chain, mitochondrial propionyl-CoA + CO2 + ATP <=> D-methylmalonyl-CoA + ADP + orthophosphate (human Reactome reaction) no propionyl_coa_catabolism Propionyl-CoA catabolism (propionate to succinyl-CoA via the methylmalonyl-CoA pathway) modules/propionyl_coa_catabolism.yaml R-HSA-71032 module_evidence "Step order and reaction stoichiometries follow the human Reactome ""Propionyl-CoA catabolism"" pathway (R-HSA-71032): R-HSA-71031 (PCC), R-HSA-71020 (MCEE), R-HSA-71010 (MMUT), with AdoCbl supply by MMAB (R-HSA-3159253) and MMAA-gated loading (R-HSA-3159259)." no purine_nucleotide_interconversion Purine nucleotide interconversion (IMP -> AMP/GMP; purine nucleotide cycle) — ADSS1/IMPDH/AMPD disorders modules/purine_nucleotide_interconversion.yaml R-HSA-111524 activity_evidence adss_step IMP + L-aspartate + GTP to adenylosuccinate + GDP + Pi REACTION adss_activity ADSS1/ADSS2: adenylosuccinate synthetase GO:0004019 adenylosuccinate synthase activity UniProtKB:Q8N142 Adenylosuccinate synthetase isozyme 1 IMP + L-Aspartate + GTP => Adenylosuccinate + GDP + Pi [ADSS] (human Reactome reaction) yes reactome/R-HSA-111524.md IMP + L-Aspartate + GTP => Adenylosuccinate + GDP + Pi [ADSS] Homo sapiens purine_nucleotide_interconversion Purine nucleotide interconversion (IMP -> AMP/GMP; purine nucleotide cycle) — ADSS1/IMPDH/AMPD disorders modules/purine_nucleotide_interconversion.yaml R-HSA-73792 activity_evidence gmps_step XMP + L-glutamine + ATP to GMP + L-glutamate + AMP + PPi REACTION gmps_activity GMPS: GMP synthase (glutamine-hydrolysing) GO:0003922 GMP synthase (glutamine-hydrolyzing) activity UniProtKB:P49915 GMP synthase [glutamine-hydrolyzing] XMP + L-Glutamine + ATP + H2O => GMP + L-Glutamate + AMP + pyrophosphate (human Reactome reaction) yes reactome/R-HSA-73792.md XMP + L-Glutamine + ATP + H2O => GMP + L-Glutamate + AMP + pyrophosphate Homo sapiens purine_nucleotide_interconversion Purine nucleotide interconversion (IMP -> AMP/GMP; purine nucleotide cycle) — ADSS1/IMPDH/AMPD disorders modules/purine_nucleotide_interconversion.yaml R-HSA-73794 activity_evidence impdh_step IMP + NAD+ + H2O to XMP + NADH REACTION impdh_activity IMPDH1/IMPDH2: IMP dehydrogenase GO:0003938 IMP dehydrogenase activity UniProtKB:P12268|UniProtKB:P20839 Inosine-5'-monophosphate dehydrogenase 2|Inosine-5'-monophosphate dehydrogenase 1 IMP + H2O + NAD+ => XMP + NADH + H+ [IMPDH1,2] (human Reactome reaction) yes reactome/R-HSA-73794.md IMP + H2O + NAD+ => XMP + NADH + H+ [IMPDH1,2] Homo sapiens purine_nucleotide_interconversion Purine nucleotide interconversion (IMP -> AMP/GMP; purine nucleotide cycle) — ADSS1/IMPDH/AMPD disorders modules/purine_nucleotide_interconversion.yaml R-HSA-73817 module_evidence Reactions follow the human Reactome purine-metabolism reactions R-HSA-111524 (ADSS), R-HSA-73794 (IMPDH), R-HSA-73792 (GMPS) and R-HSA-76590 (AMPD). yes reactome/R-HSA-73817.md Purine ribonucleoside monophosphate biosynthesis Homo sapiens purine_nucleotide_interconversion Purine nucleotide interconversion (IMP -> AMP/GMP; purine nucleotide cycle) — ADSS1/IMPDH/AMPD disorders modules/purine_nucleotide_interconversion.yaml R-HSA-76590 activity_evidence ampd_step AMP + H2O to IMP + ammonia REACTION ampd_activity AMPD1/AMPD2/AMPD3: AMP deaminase GO:0003876 AMP deaminase activity UniProtKB:P23109|UniProtKB:Q01432|UniProtKB:Q01433 AMP deaminase 1|AMP deaminase 3|AMP deaminase 2 AMP + H2O => IMP + NH4+ (AMPD) (human Reactome reaction) yes reactome/R-HSA-76590.md AMP + H2O => IMP + NH4+ (AMPD) Homo sapiens purine_salvage_and_catabolism Purine salvage and catabolism (to uric acid) — Lesch-Nyhan, ADA/PNP-SCID, xanthinuria modules/purine_salvage_and_catabolism.yaml R-HSA-112033 activity_evidence pnp_step inosine/guanosine + Pi to hypoxanthine/guanine + (deoxy)ribose-1-phosphate REACTION pnp_activity PNP: purine nucleoside phosphorylase GO:0004731 purine-nucleoside phosphorylase activity UniProtKB:P00491 Purine nucleoside phosphorylase PNP catalyzes the conversion of hypoxanthine and (deoxy)ribose-1-phosphate (human Reactome reaction) yes reactome/R-HSA-112033.md PNP catalyzes the conversion of hypoxanthine and (deoxy)ribose-1-phosphate to (deoxy)inosine Homo sapiens purine_salvage_and_catabolism Purine salvage and catabolism (to uric acid) — Lesch-Nyhan, ADA/PNP-SCID, xanthinuria modules/purine_salvage_and_catabolism.yaml R-HSA-74213 activity_evidence aprt_step adenine + PRPP to AMP + PPi REACTION aprt_activity APRT: adenine phosphoribosyltransferase GO:0003999 adenine phosphoribosyltransferase activity UniProtKB:P07741 Adenine phosphoribosyltransferase APRT catalyzes the conversion of adenine to AMP (human Reactome reaction) yes reactome/R-HSA-74213.md APRT catalyzes the conversion of adenine to AMP Homo sapiens purine_salvage_and_catabolism Purine salvage and catabolism (to uric acid) — Lesch-Nyhan, ADA/PNP-SCID, xanthinuria modules/purine_salvage_and_catabolism.yaml R-HSA-74215 activity_evidence hprt1_step hypoxanthine/guanine + PRPP to IMP/GMP + PPi REACTION hprt1_activity HPRT1: hypoxanthine-guanine phosphoribosyltransferase GO:0004422 hypoxanthine phosphoribosyltransferase activity UniProtKB:P00492 Hypoxanthine-guanine phosphoribosyltransferase HPRT1 catalyzes the conversion of guanine or hypoxanthine to GMP or IMP (human Reactome reaction) yes reactome/R-HSA-74215.md HPRT1 catalyzes the conversion of guanine or hypoxanthine to GMP or IMP Homo sapiens purine_salvage_and_catabolism Purine salvage and catabolism (to uric acid) — Lesch-Nyhan, ADA/PNP-SCID, xanthinuria modules/purine_salvage_and_catabolism.yaml R-HSA-74241 activity_evidence ada_step (deoxy)adenosine to (deoxy)inosine + NH3 REACTION ada_activity ADA: adenosine deaminase GO:0004000 adenosine deaminase activity UniProtKB:P00813 Adenosine deaminase ADA catalyzes the deamination of (deoxy)adenosine (human Reactome reaction) yes reactome/R-HSA-74241.md ADA catalyzes the deamination of (deoxy)adenosine Homo sapiens purine_salvage_and_catabolism Purine salvage and catabolism (to uric acid) — Lesch-Nyhan, ADA/PNP-SCID, xanthinuria modules/purine_salvage_and_catabolism.yaml R-HSA-74247 activity_evidence xdh_step hypoxanthine to xanthine to urate REACTION xdh_activity XDH: xanthine oxidoreductase GO:0004854 xanthine dehydrogenase activity UniProtKB:P47989 Xanthine dehydrogenase/oxidase XDH oxidizes hypoxanthine to form xanthine (human Reactome reaction) yes reactome/R-HSA-74247.md XDH oxidizes hypoxanthine to form xanthine Homo sapiens purine_salvage_and_catabolism Purine salvage and catabolism (to uric acid) — Lesch-Nyhan, ADA/PNP-SCID, xanthinuria modules/purine_salvage_and_catabolism.yaml R-HSA-74259 module_evidence Reaction stoichiometries follow the human Reactome purine salvage/catabolism reactions R-HSA-74215 (HPRT1), R-HSA-74213 (APRT), R-HSA-74241 (ADA), R-HSA-112033 (PNP) and R-HSA-74247 (XDH). yes reactome/R-HSA-74259.md Purine catabolism Homo sapiens pyruvate_metabolism Mitochondrial pyruvate fates — pyruvate dehydrogenase complex and pyruvate carboxylase modules/pyruvate_metabolism.yaml R-HSA-70268 module_evidence Reaction stoichiometries follow the human Reactome pyruvate-metabolism reactions R-HSA-9861559 (PDC synthesizes acetyl-CoA from pyruvate) and R-HSA-70501 (PC carboxylates pyruvate to oxaloacetate). yes reactome/R-HSA-70268.md Pyruvate metabolism Homo sapiens pyruvate_metabolism Mitochondrial pyruvate fates — pyruvate dehydrogenase complex and pyruvate carboxylase modules/pyruvate_metabolism.yaml R-HSA-70501 activity_evidence pc_step pyruvate + HCO3- + ATP to oxaloacetate + ADP + Pi REACTION pc_activity PC: pyruvate carboxylase (biotin-dependent) GO:0004736 pyruvate carboxylase activity UniProtKB:P11498 Pyruvate carboxylase, mitochondrial PC carboxylates PYR to OA (human Reactome reaction) no sam_cycle S-adenosylmethionine (SAM) cycle — SAM synthesis / transmethylation / SAH hydrolysis (MAT1A/GNMT/AHCY); hypermethioninemias modules/sam_cycle.yaml R-HSA-174391 activity_evidence mat_step L-methionine + ATP to S-adenosyl-L-methionine + Pi + PPi REACTION mat_activity MAT1A/MAT2A: methionine adenosyltransferase GO:0004478 methionine adenosyltransferase activity UniProtKB:Q00266 S-adenosylmethionine synthase isoform type-1 MAT1A multimers transfer Ado from ATP to L-Met (human Reactome reaction) yes reactome/R-HSA-174391.md MAT1A multimers transfer Ado from ATP to L-Met Homo sapiens sam_cycle S-adenosylmethionine (SAM) cycle — SAM synthesis / transmethylation / SAH hydrolysis (MAT1A/GNMT/AHCY); hypermethioninemias modules/sam_cycle.yaml R-HSA-174401 activity_evidence ahcy_step S-adenosyl-L-homocysteine + H2O to L-homocysteine + adenosine REACTION ahcy_activity AHCY: adenosylhomocysteinase (SAH hydrolase) GO:0004013 adenosylhomocysteinase activity UniProtKB:P23526 Adenosylhomocysteinase AHCY:NAD+ tetramer hydrolyses AdoHcy (human Reactome reaction) yes reactome/R-HSA-174401.md AHCY:NAD+ tetramer hydrolyses AdoHcy Homo sapiens sam_cycle S-adenosylmethionine (SAM) cycle — SAM synthesis / transmethylation / SAH hydrolysis (MAT1A/GNMT/AHCY); hypermethioninemias modules/sam_cycle.yaml R-HSA-6798317 activity_evidence gnmt_step S-adenosyl-L-methionine + glycine to S-adenosyl-L-homocysteine + sarcosine REACTION gnmt_activity GNMT: glycine N-methyltransferase (regulatory SAM-consumer) GO:0017174 glycine N-methyltransferase activity UniProtKB:Q14749 Glycine N-methyltransferase GNMT tetramer transfers methyl group from AdoMet to Gly to form AdoHyc (human Reactome reaction) yes reactome/R-HSA-6798317.md GNMT tetramer transfers methyl group from AdoMet to Gly to form AdoHyc and SARC Homo sapiens sex_steroid_biosynthesis Sex-steroid biosynthesis and androgen activation — HSD17B3/CYP19A1/SRD5A2 modules/sex_steroid_biosynthesis.yaml R-HSA-193048 module_evidence "The androgen steps (HSD17B3 androstenedione->testosterone; SRD5A2 testosterone->DHT) follow the human Reactome ""Androgen biosynthesis"" sub-pathway." yes reactome/R-HSA-193048.md Androgen biosynthesis Homo sapiens sex_steroid_biosynthesis Sex-steroid biosynthesis and androgen activation — HSD17B3/CYP19A1/SRD5A2 modules/sex_steroid_biosynthesis.yaml R-HSA-193060 activity_evidence cyp19a1_step C19 androgens to C18 estrogens REACTION cyp19a1_activity CYP19A1: aromatase GO:0070330 aromatase activity UniProtKB:P11511 Aromatase CYP19A1 hydroxylates ANDST to E1 (human Reactome reaction) yes reactome/R-HSA-193060.md CYP19A1 hydroxylates ANDST to E1 Homo sapiens sex_steroid_biosynthesis Sex-steroid biosynthesis and androgen activation — HSD17B3/CYP19A1/SRD5A2 modules/sex_steroid_biosynthesis.yaml R-HSA-193064 activity_evidence hsd17b3_step androstenedione to testosterone REACTION hsd17b3_activity HSD17B3: 17beta-hydroxysteroid dehydrogenase type 3 GO:0047045 testosterone dehydrogenase (NADP+) activity UniProtKB:P37058 17-beta-hydroxysteroid dehydrogenase type 3 HSD17B3-like proteins reducde ANDST to TEST (human Reactome reaction) yes reactome/R-HSA-193064.md HSD17B3-like proteins reducde ANDST to TEST Homo sapiens sex_steroid_biosynthesis Sex-steroid biosynthesis and androgen activation — HSD17B3/CYP19A1/SRD5A2 modules/sex_steroid_biosynthesis.yaml R-HSA-193143 activity_evidence cyp19a1_step C19 androgens to C18 estrogens REACTION cyp19a1_activity CYP19A1: aromatase GO:0070330 aromatase activity UniProtKB:P11511 Aromatase CYP19A1 hydroxylates TEST to EST17b (human Reactome reaction) yes reactome/R-HSA-193143.md CYP19A1 hydroxylates TEST to EST17b Homo sapiens sex_steroid_biosynthesis Sex-steroid biosynthesis and androgen activation — HSD17B3/CYP19A1/SRD5A2 modules/sex_steroid_biosynthesis.yaml R-HSA-193144 module_evidence "The aromatase reactions (CYP19A1 androstenedione->estrone, testosterone->estradiol) follow the human Reactome ""Estrogen biosynthesis"" sub-pathway." yes reactome/R-HSA-193144.md Estrogen biosynthesis Homo sapiens sex_steroid_biosynthesis Sex-steroid biosynthesis and androgen activation — HSD17B3/CYP19A1/SRD5A2 modules/sex_steroid_biosynthesis.yaml R-HSA-9705713 activity_evidence srd5a2_step testosterone to 5alpha-dihydrotestosterone (DHT) REACTION srd5a2_activity SRD5A2: steroid 5alpha-reductase type 2 GO:0003865 3-oxo-5-alpha-steroid 4-dehydrogenase activity UniProtKB:P31213 3-oxo-5-alpha-steroid 4-dehydrogenase 2 SRD5A2 dehydrogenates TEST to DHTEST (human Reactome reaction) yes reactome/R-HSA-9705713.md SRD5A2 dehydrogenates TEST to DHTEST Homo sapiens sphingolipid_de_novo_synthesis De novo sphingolipid (ceramide) biosynthesis; SPTLC1/SPTLC2/SPTSSA/KDSR/CERS1-3/DEGS1 modules/sphingolipid_de_novo_synthesis.yaml R-HSA-1660661 module_evidence "Step order and intermediates follow the human Reactome ""Sphingolipid de novo biosynthesis"" pathway (reactions R-HSA-428127 SPT, R-HSA-428123 KDSR, R-HSA-428185 CerS, R-HSA-428259 DEGS1)." yes reactome/R-HSA-1660661.md Sphingolipid de novo biosynthesis Homo sapiens sphingolipid_de_novo_synthesis De novo sphingolipid (ceramide) biosynthesis; SPTLC1/SPTLC2/SPTSSA/KDSR/CERS1-3/DEGS1 modules/sphingolipid_de_novo_synthesis.yaml R-HSA-428123 activity_evidence kdsr_step 3-ketodihydrosphingosine to dihydrosphingosine (sphinganine) REACTION kdsr_activity KDSR: 3-ketodihydrosphingosine reductase GO:0047560 3-dehydrosphinganine reductase activity UniProtKB:Q06136 3-ketodihydrosphingosine reductase KDSR reduces 3-ketosphingoid (human Reactome reaction) yes reactome/R-HSA-428123.md KDSR reduces 3-ketosphingoid Homo sapiens sphingolipid_de_novo_synthesis De novo sphingolipid (ceramide) biosynthesis; SPTLC1/SPTLC2/SPTSSA/KDSR/CERS1-3/DEGS1 modules/sphingolipid_de_novo_synthesis.yaml R-HSA-428127 activity_evidence spt_step L-serine + palmitoyl-CoA to 3-ketodihydrosphingosine PROTEIN_COMPLEX sptlc1_activity SPTLC1: serine palmitoyltransferase subunit GO:0004758 serine C-palmitoyltransferase activity UniProtKB:O15269 Serine palmitoyltransferase 1 SPTLC complexes transfer acyl-CoA onto serine (human Reactome reaction) yes reactome/R-HSA-428127.md SPTLC complexes transfer acyl-CoA onto serine Homo sapiens sphingolipid_de_novo_synthesis De novo sphingolipid (ceramide) biosynthesis; SPTLC1/SPTLC2/SPTSSA/KDSR/CERS1-3/DEGS1 modules/sphingolipid_de_novo_synthesis.yaml R-HSA-428127 activity_evidence spt_step L-serine + palmitoyl-CoA to 3-ketodihydrosphingosine PROTEIN_COMPLEX sptlc2_activity SPTLC2: PLP-binding catalytic SPT subunit GO:0004758 serine C-palmitoyltransferase activity UniProtKB:O15270 Serine palmitoyltransferase 2 SPTLC complexes transfer acyl-CoA onto serine (human Reactome reaction) yes reactome/R-HSA-428127.md SPTLC complexes transfer acyl-CoA onto serine Homo sapiens sphingolipid_de_novo_synthesis De novo sphingolipid (ceramide) biosynthesis; SPTLC1/SPTLC2/SPTSSA/KDSR/CERS1-3/DEGS1 modules/sphingolipid_de_novo_synthesis.yaml R-HSA-428185 activity_evidence cers_step sphinganine + acyl-CoA to dihydroceramide REACTION cers_activity CERS1/2/3: ceramide synthase (N-acyltransferase) GO:0050291 sphingosine N-acyltransferase activity UniProtKB:P27544|UniProtKB:Q8IU89|UniProtKB:Q96G23 Ceramide synthase 1|Ceramide synthase 3|Ceramide synthase 2 Ceramide synthases transfer acyl-CoA onto sphingoid (human Reactome reaction) yes reactome/R-HSA-428185.md Ceramide synthases transfer acyl-CoA onto sphingoid Homo sapiens sphingolipid_de_novo_synthesis De novo sphingolipid (ceramide) biosynthesis; SPTLC1/SPTLC2/SPTSSA/KDSR/CERS1-3/DEGS1 modules/sphingolipid_de_novo_synthesis.yaml R-HSA-428259 activity_evidence degs1_step dihydroceramide to ceramide (4,5-trans double bond) REACTION degs1_activity DEGS1: dihydroceramide desaturase GO:0042284 sphingolipid delta-4 desaturase activity UniProtKB:O15121 Sphingolipid delta(4)-desaturase DES1 DEGS1 dehydrogenates dihydroceramide (human Reactome reaction) yes reactome/R-HSA-428259.md DEGS1 dehydrogenates dihydroceramide Homo sapiens sterol_commitment_squalene_to_lanosterol Cholesterol biosynthesis I — sterol commitment (squalene -> lanosterol); FDFT1/SQLE/LSS modules/sterol_commitment_squalene_to_lanosterol.yaml R-HSA-191299 activity_evidence sqle_step squalene + O2 + NADPH to (S)-2,3-epoxysqualene REACTION sqle_activity SQLE: squalene monooxygenase (epoxidase) GO:0004506 squalene monooxygenase activity UniProtKB:Q14534 Squalene monooxygenase Squalene is oxidized to its epoxide (human Reactome reaction) yes reactome/R-HSA-191299.md Squalene is oxidized to its epoxide Homo sapiens sterol_commitment_squalene_to_lanosterol Cholesterol biosynthesis I — sterol commitment (squalene -> lanosterol); FDFT1/SQLE/LSS modules/sterol_commitment_squalene_to_lanosterol.yaml R-HSA-191366 activity_evidence lss_step (S)-2,3-epoxysqualene to lanosterol REACTION lss_activity LSS: lanosterol synthase (oxidosqualene cyclase) GO:0000250 lanosterol synthase activity UniProtKB:P48449 Lanosterol synthase Squalene 2,3-epoxide cyclizes, forming lanosterol (human Reactome reaction) yes reactome/R-HSA-191366.md Squalene 2,3-epoxide cyclizes, forming lanosterol Homo sapiens sterol_commitment_squalene_to_lanosterol Cholesterol biosynthesis I — sterol commitment (squalene -> lanosterol); FDFT1/SQLE/LSS modules/sterol_commitment_squalene_to_lanosterol.yaml R-HSA-191402 activity_evidence fdft1_step 2 farnesyl diphosphate + NADPH to squalene REACTION fdft1_activity FDFT1: squalene synthase GO:0051996 squalene synthase [NAD(P)H] activity UniProtKB:P37268 Squalene synthase Reduction of presqualene diphosphate to form squalene (human Reactome reaction) yes reactome/R-HSA-191402.md Reduction of presqualene diphosphate to form squalene Homo sapiens sterol_commitment_squalene_to_lanosterol Cholesterol biosynthesis I — sterol commitment (squalene -> lanosterol); FDFT1/SQLE/LSS modules/sterol_commitment_squalene_to_lanosterol.yaml R-HSA-9969896 module_evidence "Step order and reaction stoichiometries follow the human Reactome ""Lanosterol biosynthesis"" reactions R-HSA-191402 (FDFT1), R-HSA-191299 (SQLE) and R-HSA-191366 (LSS)." yes reactome/R-HSA-9969896.md Lanosterol biosynthesis Homo sapiens tetrahydrobiopterin_metabolism Tetrahydrobiopterin (BH4) biosynthesis and regeneration modules/tetrahydrobiopterin_metabolism.yaml R-HSA-1474146 activity_evidence gch1_step GTP to 7,8-dihydroneopterin 3'-triphosphate REACTION gch1_activity GCH1: GTP cyclohydrolase I GO:0003934 GTP cyclohydrolase I activity UniProtKB:P30793 GTP cyclohydrolase 1 GCH1 reduces GTP to dihydroneopterin triphosphate (human Reactome reaction) yes reactome/R-HSA-1474146.md GCH1 reduces GTP to dihydroneopterin triphosphate Homo sapiens tetrahydrobiopterin_metabolism Tetrahydrobiopterin (BH4) biosynthesis and regeneration modules/tetrahydrobiopterin_metabolism.yaml R-HSA-1474151 module_evidence Step order, compartmentalization and reaction stoichiometries follow the human Reactome BH4 pathway and its member reactions (R-HSA-1474146, R-HSA-1474184, R-HSA-1475414, R-HSA-71146, R-HSA-71130). yes reactome/R-HSA-1474151.md Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation Homo sapiens tetrahydrobiopterin_metabolism Tetrahydrobiopterin (BH4) biosynthesis and regeneration modules/tetrahydrobiopterin_metabolism.yaml R-HSA-1474184 activity_evidence pts_step 7,8-dihydroneopterin 3'-triphosphate to 6-pyruvoyltetrahydropterin REACTION pts_activity PTS/PTPS: 6-pyruvoyltetrahydropterin synthase GO:0003874 6-pyruvoyltetrahydropterin synthase activity UniProtKB:Q03393 6-pyruvoyl tetrahydrobiopterin synthase DHNTP is dephosphorylated by PTPS to PTHP (human Reactome reaction) yes reactome/R-HSA-1474184.md DHNTP is dephosphorylated by PTPS to PTHP Homo sapiens tetrahydrobiopterin_metabolism Tetrahydrobiopterin (BH4) biosynthesis and regeneration modules/tetrahydrobiopterin_metabolism.yaml R-HSA-1475414 activity_evidence spr_step 6-pyruvoyltetrahydropterin to tetrahydrobiopterin (BH4) REACTION spr_activity SPR: sepiapterin reductase GO:0004757 sepiapterin reductase (NADP+) activity UniProtKB:P35270 Sepiapterin reductase PTHP is reduced to BH4 by sepiapterin reductase (SPR) (human Reactome reaction) yes reactome/R-HSA-1475414.md PTHP is reduced to BH4 by sepiapterin reductase (SPR) Homo sapiens tetrahydrobiopterin_metabolism Tetrahydrobiopterin (BH4) biosynthesis and regeneration modules/tetrahydrobiopterin_metabolism.yaml R-HSA-71130 activity_evidence qdpr_step quinonoid dihydrobiopterin + NADH to tetrahydrobiopterin (BH4) REACTION qdpr_activity QDPR/DHPR: dihydropteridine reductase GO:0004155 6,7-dihydropteridine reductase activity UniProtKB:P09417 Dihydropteridine reductase q-dihydrobiopterin + NADH + H+ => tetrahydrobiopterin + NAD+ (human Reactome reaction) no tetrahydrobiopterin_metabolism Tetrahydrobiopterin (BH4) biosynthesis and regeneration modules/tetrahydrobiopterin_metabolism.yaml R-HSA-71146 activity_evidence pcbd1_step pterin-4a-carbinolamine to quinonoid dihydrobiopterin + H2O REACTION pcbd1_activity PCBD1/PCD: pterin-4a-carbinolamine dehydratase GO:0008124 4-alpha-hydroxytetrahydrobiopterin dehydratase activity UniProtKB:P61457|UniProtKB:Q9H0N5 Pterin-4-alpha-carbinolamine dehydratase|Pterin-4-alpha-carbinolamine dehydratase 2 4a-hydroxytetrahydrobiopterin => q-dihydrobiopterin + H2O (human Reactome reaction) no thymidylate_synthesis Thymidylate (dTMP -> dTTP) synthesis; thymidylate synthase / dUTPase / dTMP kinase modules/thymidylate_synthesis.yaml R-HSA-73605 module_evidence Reactions follow the human Reactome pyrimidine reactions R-HSA-73666 (DUT), R-HSA-73605 (TYMS) and R-HSA-73635 (DTYMK). yes reactome/R-HSA-73605.md conversion of dUMP to dTMP Homo sapiens thymidylate_synthesis Thymidylate (dTMP -> dTTP) synthesis; thymidylate synthase / dUTPase / dTMP kinase modules/thymidylate_synthesis.yaml R-HSA-73605 activity_evidence tyms_step dUMP + 5,10-methylene-THF to dTMP + dihydrofolate REACTION tyms_activity TYMS: thymidylate synthase GO:0004799 thymidylate synthase activity UniProtKB:P04818 Thymidylate synthase conversion of dUMP to dTMP (human Reactome reaction) yes reactome/R-HSA-73605.md conversion of dUMP to dTMP Homo sapiens thymidylate_synthesis Thymidylate (dTMP -> dTTP) synthesis; thymidylate synthase / dUTPase / dTMP kinase modules/thymidylate_synthesis.yaml R-HSA-73635 activity_evidence dtymk_step dTMP + ATP to dTDP + ADP REACTION dtymk_activity DTYMK: thymidylate kinase (dTMP kinase) GO:0004798 dTMP kinase activity UniProtKB:P23919 Thymidylate kinase dUMP or TMP + ATP <=> dUDP or TDP + ADP [DTYMK] (human Reactome reaction) yes reactome/R-HSA-73635.md dUMP or TMP + ATP <=> dUDP or TDP + ADP [DTYMK] Homo sapiens thymidylate_synthesis Thymidylate (dTMP -> dTTP) synthesis; thymidylate synthase / dUTPase / dTMP kinase modules/thymidylate_synthesis.yaml R-HSA-73666 activity_evidence dut_step dUTP + H2O to dUMP + diphosphate REACTION dut_activity DUT: dUTP diphosphatase (dUTPase) GO:0004170 dUTP diphosphatase activity UniProtKB:P33316 Deoxyuridine 5'-triphosphate nucleotidohydrolase hydrolysis of 2'-deoxyuridine 5'-triphosphate to form 2'-deoxyuridine 5'-monophosphate (human Reactome reaction) yes reactome/R-HSA-73666.md hydrolysis of 2'-deoxyuridine 5'-triphosphate to form 2'-deoxyuridine 5'-phosphate Homo sapiens tyrosine_catabolism L-tyrosine catabolism (hepatic tyrosine degradation to fumarate + acetoacetate) modules/tyrosine_catabolism.yaml R-HSA-71155 activity_evidence tat_step L-tyrosine + 2-oxoglutarate to 4-hydroxyphenylpyruvate + L-glutamate REACTION tat_activity TAT: tyrosine aminotransferase GO:0004838 L-tyrosine:2-oxoglutarate transaminase activity UniProtKB:P17735 Tyrosine aminotransferase TAT deaminates tyrosine (human Reactome reaction) no tyrosine_catabolism L-tyrosine catabolism (hepatic tyrosine degradation to fumarate + acetoacetate) modules/tyrosine_catabolism.yaml R-HSA-71163 activity_evidence hpd_step 4-hydroxyphenylpyruvate + O2 to homogentisate + CO2 REACTION hpd_activity HPD/HPPD: 4-hydroxyphenylpyruvate dioxygenase GO:0003868 4-hydroxyphenylpyruvate dioxygenase activity UniProtKB:P32754 4-hydroxyphenylpyruvate dioxygenase HPD dioxygenates HPP (human Reactome reaction) no tyrosine_catabolism L-tyrosine catabolism (hepatic tyrosine degradation to fumarate + acetoacetate) modules/tyrosine_catabolism.yaml R-HSA-71164 activity_evidence hgd_step homogentisate + O2 to 4-maleylacetoacetate REACTION hgd_activity HGD: homogentisate 1,2-dioxygenase GO:0004411 homogentisate 1,2-dioxygenase activity UniProtKB:Q93099 Homogentisate 1,2-dioxygenase HGD dioxygenates homogentisate (human Reactome reaction) no tyrosine_catabolism L-tyrosine catabolism (hepatic tyrosine degradation to fumarate + acetoacetate) modules/tyrosine_catabolism.yaml R-HSA-71173 activity_evidence gstz1_step 4-maleylacetoacetate to 4-fumarylacetoacetate REACTION gstz1_activity GSTZ1/MAAI: maleylacetoacetate isomerase GO:0016034 maleylacetoacetate isomerase activity UniProtKB:O43708 Maleylacetoacetate isomerase GSTZ1 isomerizes 4-MAA (human Reactome reaction) no tyrosine_catabolism L-tyrosine catabolism (hepatic tyrosine degradation to fumarate + acetoacetate) modules/tyrosine_catabolism.yaml R-HSA-71181 activity_evidence fah_step 4-fumarylacetoacetate to fumarate + acetoacetate REACTION fah_activity FAH: fumarylacetoacetate hydrolase GO:0004334 fumarylacetoacetase activity UniProtKB:P16930 Fumarylacetoacetate hydrolase FAH cleaves 4FAA (human Reactome reaction) no tyrosine_catabolism L-tyrosine catabolism (hepatic tyrosine degradation to fumarate + acetoacetate) modules/tyrosine_catabolism.yaml R-HSA-8963684 module_evidence "Step order and reaction stoichiometries follow the human Reactome ""Tyrosine catabolism"" pathway (R-HSA-8963684) and its member reactions (R-HSA-71155, R-HSA-71163, R-HSA-71164, R-HSA-71173, R-HSA-71181)." no urea_cycle Urea cycle (vertebrate hepatic ureagenesis, Krebs-Henseleit cycle) modules/urea_cycle.yaml R-HSA-372448 activity_evidence citrin_aspartate_supply mitochondrial aspartate export for the ASS1 step (SLC25A13, citrin) TRANSPORT_STEP slc25a13_activity SLC25A13/citrin: aspartate/glutamate antiporter GO:0015183 L-aspartate transmembrane transporter activity UniProtKB:O75746|UniProtKB:Q9UJS0 Electrogenic aspartate/glutamate antiporter SLC25A12, mitochondrial|Electrogenic aspartate/glutamate antiporter SLC25A13, mitochondrial SLC25A12,13 exchange L-Glu and L-Asp (human Reactome reaction) yes reactome/R-HSA-372448.md SLC25A12,13 exchange L-Glu and L-Asp Homo sapiens urea_cycle Urea cycle (vertebrate hepatic ureagenesis, Krebs-Henseleit cycle) modules/urea_cycle.yaml R-HSA-70542 activity_evidence nags_step L-glutamate + acetyl-CoA to N-acetyl-L-glutamate + CoA REGULATORY_STEP nags_activity NAGS: N-acetylglutamate synthase GO:0004042 L-glutamate N-acetyltransferase activity, acting on acetyl-CoA as donor UniProtKB:Q8N159 N-acetylglutamate synthase, mitochondrial glutamate + acetyl CoA => N-acetyl glutamate + CoA (human Reactome reaction) no urea_cycle Urea cycle (vertebrate hepatic ureagenesis, Krebs-Henseleit cycle) modules/urea_cycle.yaml R-HSA-70555 activity_evidence cps1_step NH3 + HCO3- + 2 ATP to carbamoyl phosphate + 2 ADP + Pi REACTION cps1_activity CPS1: carbamoyl-phosphate synthetase 1 GO:0004087 carbamoyl-phosphate synthase (ammonia) activity UniProtKB:P31327 Carbamoyl-phosphate synthase [ammonia], mitochondrial 2 ATP + NH4+ + HCO3- => 2 ADP + orthophosphate + carbamoyl phosphate (human Reactome reaction) no urea_cycle Urea cycle (vertebrate hepatic ureagenesis, Krebs-Henseleit cycle) modules/urea_cycle.yaml R-HSA-70560 activity_evidence otc_step carbamoyl phosphate + L-ornithine to L-citrulline + Pi REACTION otc_activity OTC: ornithine transcarbamylase GO:0004585 ornithine carbamoyltransferase activity UniProtKB:P00480 Ornithine transcarbamylase, mitochondrial carbamoyl phosphate + ornithine => citrulline + orthophosphate (human Reactome reaction) no urea_cycle Urea cycle (vertebrate hepatic ureagenesis, Krebs-Henseleit cycle) modules/urea_cycle.yaml R-HSA-70569 activity_evidence arg1_step L-arginine + H2O to L-ornithine + urea REACTION arg1_activity ARG1: arginase 1 GO:0004053 arginase activity UniProtKB:P05089|UniProtKB:P78540 Arginase-1|Arginase-2, mitochondrial arginine + H2O => ornithine + urea [ARG1] (human Reactome reaction) yes reactome/R-HSA-70569.md arginine + H2O => ornithine + urea [ARG1] Homo sapiens urea_cycle Urea cycle (vertebrate hepatic ureagenesis, Krebs-Henseleit cycle) modules/urea_cycle.yaml R-HSA-70573 activity_evidence asl_step argininosuccinate to L-arginine + fumarate REACTION asl_activity ASL: argininosuccinate lyase GO:0004056 argininosuccinate lyase activity UniProtKB:P04424 Argininosuccinate lyase argininosuccinate <=> fumarate + arginine (human Reactome reaction) no urea_cycle Urea cycle (vertebrate hepatic ureagenesis, Krebs-Henseleit cycle) modules/urea_cycle.yaml R-HSA-70577 activity_evidence ass1_step L-citrulline + L-aspartate + ATP to argininosuccinate + AMP + PPi REACTION ass1_activity ASS1: argininosuccinate synthase GO:0004055 argininosuccinate synthase activity UniProtKB:P00966 Argininosuccinate synthase ASS1 tetramer transforms L-Asp and L-Cit to argininosuccinate (human Reactome reaction) yes reactome/R-HSA-70577.md ASS1 tetramer:NMRAL1 dimer:NADPH transforms L-Asp and L-Cit to ARSUA Homo sapiens urea_cycle Urea cycle (vertebrate hepatic ureagenesis, Krebs-Henseleit cycle) modules/urea_cycle.yaml R-HSA-70634 activity_evidence ornithine_citrulline_transport citrulline export / ornithine import across the inner membrane (SLC25A15) TRANSPORT_STEP slc25a15_activity SLC25A15/ORNT1: ornithine/citrulline antiporter GO:0000064 L-ornithine transmembrane transporter activity UniProtKB:Q9BXI2|UniProtKB:Q9Y619 Mitochondrial ornithine transporter 2|Mitochondrial ornithine transporter 1 ornithine (cytosolic) + citrulline (mitochondrial) => ornithine (mitochondrial) (human Reactome reaction) no urea_cycle Urea cycle (vertebrate hepatic ureagenesis, Krebs-Henseleit cycle) modules/urea_cycle.yaml R-HSA-70635 module_evidence "The step order, compartmentalization and reaction stoichiometries follow the human Reactome ""Urea cycle"" pathway (R-HSA-70635) and its member reactions (R-HSA-70542, R-HSA-70555, R-HSA-70560, R-HSA-70634, R-HSA-70577, R-HSA-70573, R-HSA-70569, R-HSA-372448)." yes reactome/R-HSA-70635.md Urea cycle Homo sapiens wnt_signaling Generic Wnt signaling pathway module modules/wnt_signaling.yaml R-HSA-195721 module_evidence Reactome represents Wnt signaling as a set of conserved subpathways spanning ligand biogenesis, receptor activation, and downstream transcriptional and non-canonical responses. no wnt_signaling Generic Wnt signaling pathway module modules/wnt_signaling.yaml R-HSA-201681 module_evidence Reactome models the canonical output as TCF/LEF-dependent transcription driven by stabilized beta-catenin. no