Tricarboxylic acid cycle

A taxon-neutral module for the oxidative tricarboxylic acid (TCA) cycle, covering acetyl-CoA entry through citrate synthase, citrate/isocitrate interconversion by aconitase, oxidative decarboxylation of isocitrate to 2-oxoglutarate and of 2-oxoglutarate to succinyl-CoA, substrate-level phosphorylation by succinyl-CoA ligase, succinate oxidation by respiratory complex II, fumarate hydration, and malate oxidation to regenerate oxaloacetate. The chemistry is conserved between bacteria, where the cycle runs in the cytoplasm and complex II sits in the plasma membrane, and eukaryotes, where it runs in the mitochondrial matrix and complex II sits in the inner mitochondrial membrane. The enzyme implementations differ at several steps: citrate synthase is a hexameric type II enzyme in many Gram-negative bacteria and a dimeric type I enzyme in mitochondria; the isocitrate step uses NADP-dependent isocitrate dehydrogenases in many bacteria but an allosterically regulated NAD-dependent hetero-oligomeric isocitrate dehydrogenase in eukaryotic mitochondria; the eukaryotic 2-oxoglutarate dehydrogenase complex carries an extra adaptor subunit that recruits the E3 component; and malate can be oxidized by NAD-dependent malate dehydrogenase or by membrane-associated malate:quinone oxidoreductases. Paralogous isozymes in other compartments (peroxisomal or cytosolic citrate synthase, malate dehydrogenase and NADP-isocitrate dehydrogenase) serve the glyoxylate cycle, NADPH supply or redox shuttles rather than the oxidative cycle.

MODULE:tca_cycleDRAFTCONCRETEMetabolic Pathwaymodules/tca_cycle.yaml
tricarboxylic acid cycleGO:0006099
GO:0006099
tricarboxylic acid cycle
GO represents the TCA cycle as the pathway that oxidizes acetyl-CoA to CO2 while generating reducing equivalents and regenerating oxaloacetate.
YeastPathways:TCA-EUK-PWY
TCA cycle, aerobic respiration (S. cerevisiae, SGD YeastPathways)
YeastCyc lists the eight cycle reactions with CIT1/CIT2/CIT3, ACO1/ACO2, IDH1/IDH2, KGD1/KGD2/LPD1, LSC1/LSC2, SDH1-4 plus YJL045W, FUM1 and MDH1/MDH2/MDH3, and also includes pyruvate carboxylase (PYC1/PYC2). After review the oxidative-cycle catalysts retained here are CIT1 and CIT3, ACO1, IDH1/IDH2, KGD1/KGD2/LPD1 plus KGD4, LSC1/LSC2, SDH1-4, FUM1 and MDH1. CIT2 and MDH3 are peroxisomal and MDH2 cytosolic (glyoxylate cycle and gluconeogenesis), ACO2 is a homocitrate dehydratase of lysine biosynthesis, and pyruvate carboxylase is an anaplerotic input modelled in pyruvate_metabolism.
YeastPathways:PWY-5084
2-oxoglutarate decarboxylation to succinyl-CoA (S. cerevisiae, SGD YeastPathways)
YeastCyc splits the 2-oxoglutarate dehydrogenase complex into its E1 (KGD1), E2 (KGD2) and E3 (LPD1) half-reactions; this frame is the oxoglutarate_dehydrogenase_complex_step submodule here. The E3-recruiting subunit KGD4 is not listed by YeastCyc and was added.
YeastPathways:PWY3O-94
superpathway of TCA cycle and glyoxylate cycle (S. cerevisiae, SGD YeastPathways)
Superpathway frame combining the TCA cycle with the isocitrate lyase and malate synthase bypass. The TCA reactions are modelled here; the bypass is the separate glyoxylate_cycle module.
PMID:9140965
The CIT3 gene of Saccharomyces cerevisiae encodes a second mitochondrial isoform of citrate synthase.
CIT3 encodes an active, mitochondrially imported citrate synthase that contributes to respiratory growth in a cit1 background.
PMID:2181273
Citrate synthase encoded by the CIT2 gene of Saccharomyces cerevisiae is peroxisomal.
The major citrate synthase activity is mitochondrial (CIT1), whereas the CIT2 enzyme is peroxisomal and participates in the glyoxylate cycle.
PMID:15975908
Yeast aconitase in two locations and two metabolic pathways: seeing small amounts is believing.
Yeast Aco1 is distributed between mitochondria, where it functions in the TCA cycle, and the cytosol, where it functions in the glyoxylate shunt.
PMID:23106124
The fungal α-aminoadipate pathway for lysine biosynthesis requires two enzymes of the aconitase family for the isomerization of homocitrate to homoisocitrate.
Yeast Aco1p is essential for the citric acid cycle, while Aco2p specifically and exclusively contributes to lysine biosynthesis as a homocitrate dehydratase; ACO2 is therefore not a TCA-cycle aconitase.
PMID:1939242
NAD(+)-dependent isocitrate dehydrogenase. Cloning, nucleotide sequence, and disruption of the IDH2 gene from Saccharomyces cerevisiae.
IDH2 is essential for NAD-dependent isocitrate dehydrogenase activity and its loss abolishes growth on acetate, consistent with an essential role in the oxidative citric acid cycle.
PMID:1644826
Cloning and characterization of the gene encoding the IDH1 subunit of NAD(+)-dependent isocitrate dehydrogenase from Saccharomyces cerevisiae.
IDH1 is also essential for a functional NAD-dependent isocitrate dehydrogenase; both subunits are required.
PMID:8369302
Kinetic analysis of NAD(+)-isocitrate dehydrogenase with altered isocitrate binding sites: contribution of IDH1 and IDH2 subunits to regulation and catalysis.
The octameric IDH1/IDH2 enzyme is AMP-activated; IDH1 acts as the regulatory subunit and IDH2 as the catalytic subunit.
PMID:8099357
Function and expression of yeast mitochondrial NAD- and NADP-specific isocitrate dehydrogenases.
NAD-IDH is required for mitochondrial respiration with citrate, whereas the mitochondrial NADP-IDH (IDP1) does not participate in TCA-cycle based respiration despite its location.
PMID:15574419
Kinetic properties and metabolic contributions of yeast mitochondrial and cytosolic NADP+-specific isocitrate dehydrogenases.
Metabolite measurements in mutants indicate that major cellular isocitrate flux is through NAD-IDH in glucose-grown cells, and through cytosolic IDP2 on nonfermentable carbon sources, so NADP-IDHs contribute 2-oxoglutarate outside the mitochondrial cycle.
PMID:2503710
Structure and regulation of KGD1, the structural gene for yeast alpha-ketoglutarate dehydrogenase.
KGD1 encodes the E1 component of the yeast 2-oxoglutarate dehydrogenase complex; its disruption abolishes complex activity.
PMID:2072900
In vivo assembly of yeast mitochondrial alpha-ketoglutarate dehydrogenase complex.
KGD1 (E1), KGD2 (E2 core) and the shared E3 assemble into the mitochondrial 2-oxoglutarate dehydrogenase complex.
PMID:25165143
The novel component Kgd4 recruits the E3 subunit to the mitochondrial α-ketoglutarate dehydrogenase.
Kgd4 (Ymr31/MRPS36) binds both the E1-E2 core and E3 and acts as a conserved molecular adaptor needed for a stable fungal and animal 2-oxoglutarate dehydrogenase complex.
PMID:9874242
Genes of succinyl-CoA ligase from Saccharomyces cerevisiae.
LSC1 (alpha) and LSC2 (beta) are both required for mitochondrial succinyl-CoA ligase activity, and the yeast enzyme uses ATP but not GTP.
PMID:11803020
The Saccharomyces cerevisiae mitochondrial succinate:ubiquinone oxidoreductase.
Review of the four-subunit yeast complex II (SDH1-SDH4), structurally and catalytically similar to other succinate:quinone oxidoreductases.
PMID:11585823
Mitochondrial and cytosolic isoforms of yeast fumarase are derivatives of a single translation product and have identical amino termini.
A single FUM1 translation product is distributed between mitochondria and cytosol; the mitochondrial pool is the TCA-cycle enzyme.
PMID:1986231
Isolation, nucleotide sequence analysis, and disruption of the MDH2 gene from Saccharomyces cerevisiae: evidence for three isozymes of yeast malate dehydrogenase.
Yeast has a mitochondrial (MDH1), a nonmitochondrial (MDH2) and a third malate dehydrogenase isozyme; MDH2 is needed for growth on acetate or ethanol, i.e. outside the mitochondrial cycle.
file:genes/PSEPK/gltA/gltA-ai-review.yaml
PSEPK gltA gene review
PSEPK GltA is a curated citrate synthase and marks acetyl-CoA entry into the KT2440 TCA cycle.
file:genes/PSEPK/sdhA/sdhA-ai-review.yaml
PSEPK sdhA gene review
PSEPK SdhA is curated as the catalytic flavoprotein subunit of succinate dehydrogenase, connecting the TCA cycle to the respiratory quinone pool.
file:genes/ECOLI/sucA/sucA-ai-review.yaml
ECOLI sucA gene review
E. coli SucA grounds the 2-oxoglutarate dehydrogenase E1 role in the bacterial oxoglutarate dehydrogenase complex.
file:genes/ECOLI/sucB/sucB-ai-review.yaml
ECOLI sucB gene review
E. coli SucB grounds the E2 succinyltransferase role in the bacterial oxoglutarate dehydrogenase complex.
file:genes/ECOLI/lpd/lpd-ai-review.yaml
ECOLI lpd gene review
E. coli LpdA grounds the shared E3 dihydrolipoyl dehydrogenase role used by the bacterial oxoglutarate dehydrogenase complex.
file:genes/yeast/IDP1/IDP1-ai-review.yaml
IDP1 gene review (S. cerevisiae)
The IDP1 review curates the mitochondrial NADP-IDH as an isocitrate metabolism and NADP enzyme distinct from the TCA-cycle NAD-IDH, which is why IDP1 is not a member of this module.
file:human/SUCLA2/SUCLA2-ai-review.yaml
SUCLA2 gene review (human)
Human SUCLA2 (UniProtKB:Q9P2R7) is curated as the ATP-specific beta subunit of mitochondrial succinyl-CoA synthetase (GO:0004775, in GO:0009361), and is listed as a eukaryotic representative of the beta-subunit family at the succinyl-CoA to succinate step.
file:modules/tca_cycle-deep-research-openscientist.md
OpenScientist module research for the TCA cycle
The generic module-level research supports the oxidative TCA-cycle boundary, including bacterial variants at fumarase and malate oxidation and treating pyruvate carboxylase as an anaplerotic input rather than a cyclic reaction.
file:projects/P_PUTIDA/deep-research/PSEPK__tca_cycle__ppu00020-deep-research-openscientist.md
OpenScientist PSEPK/ppu00020 TCA-cycle research
The P. putida KT2440 pathway report concludes that the oxidative TCA cycle is satisfiable, with quinone-linked MQO as the primary malate oxidation branch and with scpC/prpC treated as methylcitrate or CoA-transferase boundary cases rather than core SCS/citrate synthase replacements.

Reusable boundary: this module describes the oxidative TCA cycle and its immediate bacterial and eukaryotic alternatives, not every KEGG ppu00020 or YeastCyc neighbor. Pyruvate dehydrogenase supplies acetyl-CoA upstream and pyruvate carboxylase supplies an external anaplerotic oxaloacetate input (both in pyruvate_metabolism); the isocitrate lyase/malate synthase bypass is glyoxylate_cycle; methylcitrate/propionyl-CoA CoA-transferase proteins are adjacent propionate-metabolism context. The PSEPK instantiation is satisfiable with gltA/Q88FA4, acnB/Q88KF1 plus acnA-I/Q88L24, icd/Q88FS2 plus idh/Q88FS1, sucA/Q88FA9-sucB/Q88FB0 with lpdG/Q88FB1 or related E3 components, sucD/Q88FB3-sucC/Q88FB2, sdhABCD/Q88FA7-Q88FA8-Q88FA5-Q88FA6, fumarase paralogs including the class-I enzyme PP_0897/Q88PF3 and the class-II enzymes fumC/Q88M20 and fumC-I/Q88PA6, and malate oxidation by mqo1/Q88PU7, mqo2/Q88NF9, mqo3/Q88IS4, and/or mdh/Q88Q44. ALIGN (YeastPathways project, 2026-10): S. cerevisiae and S. pombe mitochondrial exemplars were added at every step, with two lineage variant sets (type II bacterial versus type I eukaryotic citrate synthase, which fall in different PANTHER families PTHR42871 and PTHR11739; NADP-IDH of bacteria versus the NAD-IDH IDH1/IDH2 hetero-octamer of mitochondria), an optional eukaryotic Kgd4 adaptor part in the 2-oxoglutarate dehydrogenase complex, and both plasma-membrane (bacterial) and inner-mitochondrial-membrane (eukaryotic) locations for complex II. PANTHER family ids were added only where every representative falls in the same family (verified against the UniProt PANTHER cross-references and interpro/panther/panther.obo); the aconitase, fumarase, SdhD/Sdh4 and malate dehydrogenase descriptors stay without an id because their bacterial and eukaryotic representatives fall in different families. YeastCyc corrections: ACO2 is removed from the aconitase step because Aco2p is a homocitrate dehydratase used only in lysine biosynthesis (PMID:23106124; consistent with lysine_biosynthesis_aminoadipate); CIT2 (peroxisomal), MDH2 (cytosolic) and MDH3 (peroxisomal) belong to the glyoxylate cycle and gluconeogenesis rather than the mitochondrial cycle; KGD4 was added as the E3-recruiting subunit of the 2-oxoglutarate dehydrogenase complex; the poorly characterized SDH1 paralog YJL045W (SDH1b/SDH9) and the SDH3/SDH4 paralogs SHH3 and SHH4 were not added as exemplars. The mitochondrial NADP-IDH IDP1 is not a TCA-cycle member: it does not support TCA-based respiration (PMID:8099357), and the major isocitrate flux on glucose is through NAD-IDH, while cytosolic IDP2 carries it on nonfermentable carbon (PMID:15574419). GO-CAM disagreements: the YeastPathways TCA-EUK-PWY conversion enables MALATE-DEH-RXN by MAE1 (malic enzyme) and MDH1 rather than by MDH1 alone, places both aconitase activities in the cytosol, enables CITSYN-RXN by CIT2 as well as CIT1/CIT3, includes pyruvate carboxylase, and types every activity as part of the generic aerobic respiration process; the PWY3O-94 superpathway conversion places all activities, including complex II, in the cytosol or plasma membrane. The PomBase model 665912ed00000015 types aco2 (Q9P7D4, which UniProt annotates as a homocitrate dehydratase-mitoribosomal bL21m fusion) as a TCA aconitase, places dld1 in pyruvate decarboxylation rather than the 2-oxoglutarate dehydrogenase step, types sdh1 with succinate dehydrogenase (FAD) activity (GO:0160308) rather than the quinone-reducing complex activity, and includes NADP-IDH idp1, isocitrate lyase (SPBC1683.11c), glyoxylate reductase, fumarate reductase, oxaloacetate tautomerase, lipoylation and thiamine-pyrophosphate transport activities that lie outside this module.

17Nodes
12Parts
2Variant Sets
4Variants
14Annotons
8Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • tca_cycle-deep-research-openscientist.md (openscientist)

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

  • citrate_synthase_step → aconitate_hydratase_step [NOT_CHECKED]
  • aconitate_hydratase_step → isocitrate_dehydrogenase_step [NOT_CHECKED]
  • isocitrate_dehydrogenase_step → oxoglutarate_dehydrogenase_complex_step [NOT_CHECKED]
  • oxoglutarate_dehydrogenase_complex_step → succinate_coa_ligase_step [NOT_CHECKED]
  • succinate_coa_ligase_step → succinate_dehydrogenase_step [NOT_CHECKED]
  • succinate_dehydrogenase_step → fumarate_hydratase_step [NOT_CHECKED]
  • fumarate_hydratase_step → malate_to_oxaloacetate_step [NOT_CHECKED]
  • malate_to_oxaloacetate_step → citrate_synthase_step [NOT_CHECKED]

Function consistency and core coverage

39 gene-function check(s) reflected in core functions · 0 conflict(s) · 6 evidence or coverage gap(s) (76 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
citrate_synthase_activity gltA (Pseudomonas putida KT2440)
UniProtKB:Q88FA4
Family Representative 		citrate synthase activity
GO:0036440 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mitochondrial_citrate_synthase_activity CIT1 (Saccharomyces cerevisiae)
UniProtKB:P00890
Family Representative 		citrate synthase activity
GO:0036440 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mitochondrial_citrate_synthase_activity CIT3 (Saccharomyces cerevisiae)
UniProtKB:P43635
Family Representative 		citrate synthase activity
GO:0036440 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mitochondrial_citrate_synthase_activity cit1 (Schizosaccharomyces pombe)
UniProtKB:Q10306
Family Representative 		citrate synthase activity
GO:0036440 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aconitate_hydratase_activity acnA-I (Pseudomonas putida KT2440)
UniProtKB:Q88L24
Family Representative 		aconitate hydratase activity
GO:0003994 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aconitate_hydratase_activity acnB (Pseudomonas putida KT2440)
UniProtKB:Q88KF1
Family Representative 		aconitate hydratase activity
GO:0003994 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aconitate_hydratase_activity ACO1 (Saccharomyces cerevisiae)
UniProtKB:P19414
Family Representative 		aconitate hydratase activity
GO:0003994 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aconitate_hydratase_activity aco1 (Schizosaccharomyces pombe)
UniProtKB:O13966
Family Representative 		aconitate hydratase activity
GO:0003994 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
isocitrate_dehydrogenase_nadp_activity icd (Pseudomonas putida KT2440)
UniProtKB:Q88FS2
Family Representative 		isocitrate dehydrogenase (NADP+) activity
GO:0004450 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
isocitrate_dehydrogenase_nadp_activity idh (Pseudomonas putida KT2440)
UniProtKB:Q88FS1
Family Representative 		isocitrate dehydrogenase (NADP+) activity
GO:0004450 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
isocitrate_dehydrogenase_nad_activity PROTEIN_COMPLEX
Gene 		isocitrate dehydrogenase (NAD+) activity
GO:0004449 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
oxoglutarate_dehydrogenase_activity sucA (Pseudomonas putida KT2440)
UniProtKB:Q88FA9
Family Representative 		oxoglutarate dehydrogenase (succinyl-transferring) activity
GO:0004591 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
oxoglutarate_dehydrogenase_activity sucA (Escherichia coli K-12)
UniProtKB:P0AFG3
Family Representative 		oxoglutarate dehydrogenase (succinyl-transferring) activity
GO:0004591 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
oxoglutarate_dehydrogenase_activity KGD1 (Saccharomyces cerevisiae)
UniProtKB:P20967
Family Representative 		oxoglutarate dehydrogenase (succinyl-transferring) activity
GO:0004591 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
oxoglutarate_dehydrogenase_activity kgd1 (Schizosaccharomyces pombe)
UniProtKB:O74378
Family Representative 		oxoglutarate dehydrogenase (succinyl-transferring) activity
GO:0004591 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dihydrolipoyl_succinyltransferase_activity sucB (Pseudomonas putida KT2440)
UniProtKB:Q88FB0
Family Representative 		dihydrolipoyllysine-residue succinyltransferase activity
GO:0004149 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dihydrolipoyl_succinyltransferase_activity sucB (Escherichia coli K-12)
UniProtKB:P0AFG6
Family Representative 		dihydrolipoyllysine-residue succinyltransferase activity
GO:0004149 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dihydrolipoyl_succinyltransferase_activity KGD2 (Saccharomyces cerevisiae)
UniProtKB:P19262
Family Representative 		dihydrolipoyllysine-residue succinyltransferase activity
GO:0004149 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dihydrolipoyl_succinyltransferase_activity kgd2 (Schizosaccharomyces pombe)
UniProtKB:O94681
Family Representative 		dihydrolipoyllysine-residue succinyltransferase activity
GO:0004149 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dihydrolipoyl_dehydrogenase_activity lpdG (Pseudomonas putida KT2440)
UniProtKB:Q88FB1
Family Representative 		dihydrolipoyl dehydrogenase (NADH) activity
GO:0004148 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dihydrolipoyl_dehydrogenase_activity lpd (Escherichia coli K-12)
UniProtKB:P0A9P0
Family Representative 		dihydrolipoyl dehydrogenase (NADH) activity
GO:0004148 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dihydrolipoyl_dehydrogenase_activity LPD1 (Saccharomyces cerevisiae)
UniProtKB:P09624
Family Representative 		dihydrolipoyl dehydrogenase (NADH) activity
GO:0004148 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dihydrolipoyl_dehydrogenase_activity dld1 (Schizosaccharomyces pombe)
UniProtKB:O00087
Family Representative 		dihydrolipoyl dehydrogenase (NADH) activity
GO:0004148 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
kgd4_adaptor_activity KGD4 / YMR31 (Saccharomyces cerevisiae)
UniProtKB:P19955
Family Representative 		protein-macromolecule adaptor activity
GO:0030674 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
kgd4_adaptor_activity kgd4 (Schizosaccharomyces pombe)
UniProtKB:G2TRP3
Family Representative 		protein-macromolecule adaptor activity
GO:0030674 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
succinate_coa_ligase_adp_activity PROTEIN_COMPLEX
Gene 		succinate-CoA ligase (ADP-forming) activity
GO:0004775 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
succinate_dehydrogenase_quinone_activity PROTEIN_COMPLEX
Gene 		succinate dehydrogenase (quinone) activity
GO:0008177 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
succinate_dehydrogenase_quinone_activity/sdha_flavoprotein_unit sdhA (Pseudomonas putida KT2440)
UniProtKB:Q88FA7
Family Representative 		succinate dehydrogenase activity
GO:0000104 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
succinate_dehydrogenase_quinone_activity/sdha_flavoprotein_unit SDH1 (Saccharomyces cerevisiae)
UniProtKB:Q00711
Family Representative 		succinate dehydrogenase activity
GO:0000104 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
succinate_dehydrogenase_quinone_activity/sdha_flavoprotein_unit sdh1 (Schizosaccharomyces pombe)
UniProtKB:Q9UTJ7
Family Representative 		succinate dehydrogenase activity
GO:0000104 		Annotation Supported
A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it.
succinate_dehydrogenase_quinone_activity/sdhb_iron_sulfur_unit sdhB (Pseudomonas putida KT2440)
UniProtKB:Q88FA8
Family Representative 		electron transfer activity
GO:0009055 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
succinate_dehydrogenase_quinone_activity/sdhb_iron_sulfur_unit SDH2 (Saccharomyces cerevisiae)
UniProtKB:P21801
Family Representative 		electron transfer activity
GO:0009055 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
succinate_dehydrogenase_quinone_activity/sdhb_iron_sulfur_unit sdh2 (Schizosaccharomyces pombe)
UniProtKB:P21911
Family Representative 		electron transfer activity
GO:0009055 		Non Core Supported
The review explicitly retains this function as non-core; promotion into core_functions is not implied.
fumarate_hydratase_activity PP_0897 (Pseudomonas putida KT2440)
UniProtKB:Q88PF3
Family Representative 		fumarate hydratase activity
GO:0004333 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fumarate_hydratase_activity fumC-I (Pseudomonas putida KT2440)
UniProtKB:Q88PA6
Family Representative 		fumarate hydratase activity
GO:0004333 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fumarate_hydratase_activity fumC (Pseudomonas putida KT2440)
UniProtKB:Q88M20
Family Representative 		fumarate hydratase activity
GO:0004333 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fumarate_hydratase_activity FUM1 (Saccharomyces cerevisiae)
UniProtKB:P08417
Family Representative 		fumarate hydratase activity
GO:0004333 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fumarate_hydratase_activity fum1 (Schizosaccharomyces pombe)
UniProtKB:O94552
Family Representative 		fumarate hydratase activity
GO:0004333 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
malate_dehydrogenase_nad_activity mdh (Pseudomonas putida KT2440)
UniProtKB:Q88Q44
Family Representative 		L-malate dehydrogenase (NAD+) activity
GO:0030060 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
malate_dehydrogenase_nad_activity MDH1 (Saccharomyces cerevisiae)
UniProtKB:P17505
Family Representative 		L-malate dehydrogenase (NAD+) activity
GO:0030060 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
malate_dehydrogenase_nad_activity mdh1 (Schizosaccharomyces pombe)
UniProtKB:Q9Y7R8
Family Representative 		L-malate dehydrogenase (NAD+) activity
GO:0030060 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
malate_dehydrogenase_quinone_activity mqo1 (Pseudomonas putida KT2440)
UniProtKB:Q88PU7
Family Representative 		L-malate dehydrogenase (quinone) activity
GO:0008924 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
malate_dehydrogenase_quinone_activity mqo2 (Pseudomonas putida KT2440)
UniProtKB:Q88NF9
Family Representative 		L-malate dehydrogenase (quinone) activity
GO:0008924 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
malate_dehydrogenase_quinone_activity mqo3 (Pseudomonas putida KT2440)
UniProtKB:Q88IS4
Family Representative 		L-malate dehydrogenase (quinone) activity
GO:0008924 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
citrate_synthase_activity bacterial type II citrate synthase family (GltA)
PANTHER:PTHR42871
Family 		citrate synthase activity
GO:0036440 		Family Supported
Family review supports GO:0036440 FAMILY_WIDE. Asserted by tca_cycle for P. putida GltA; accepted by both reviewed members.
mitochondrial_citrate_synthase_activity eukaryotic type I citrate synthase family
PANTHER:PTHR11739:SF8
Family 		citrate synthase activity
GO:0036440 		Family Supported
Family review supports GO:0036440 for PANTHER:PTHR11739:SF8. Citrate synthase subfamilies, as tca_cycle asserts on the base family. PrpC (SF25) is included because it retains citrate synthase activity as a minor component; for SF25 the term is secondary and non-core, and 2-methylcitrate synthase is the physiological activity.
mitochondrial_citrate_synthase_activity eukaryotic type I citrate synthase family
PANTHER:PTHR11739:SF4
Family 		citrate synthase activity
GO:0036440 		Family Supported
Family review supports GO:0036440 for PANTHER:PTHR11739:SF4. Citrate synthase subfamilies, as tca_cycle asserts on the base family. PrpC (SF25) is included because it retains citrate synthase activity as a minor component; for SF25 the term is secondary and non-core, and 2-methylcitrate synthase is the physiological activity.
mitochondrial_citrate_synthase_activity eukaryotic type I citrate synthase family
PANTHER:PTHR11739:SF15
Family 		citrate synthase activity
GO:0036440 		Family Supported
Family review supports GO:0036440 for PANTHER:PTHR11739:SF15. Citrate synthase subfamilies, as tca_cycle asserts on the base family. PrpC (SF25) is included because it retains citrate synthase activity as a minor component; for SF25 the term is secondary and non-core, and 2-methylcitrate synthase is the physiological activity.
mitochondrial_citrate_synthase_activity eukaryotic type I citrate synthase family
PANTHER:PTHR11739:SF23
Family 		citrate synthase activity
GO:0036440 		Family Supported
Family review supports GO:0036440 for PANTHER:PTHR11739:SF23. Citrate synthase subfamilies, as tca_cycle asserts on the base family. PrpC (SF25) is included because it retains citrate synthase activity as a minor component; for SF25 the term is secondary and non-core, and 2-methylcitrate synthase is the physiological activity.
mitochondrial_citrate_synthase_activity eukaryotic type I citrate synthase family
PANTHER:PTHR11739:SF11
Family 		citrate synthase activity
GO:0036440 		Family Supported
Family review supports GO:0036440 for PANTHER:PTHR11739:SF11. Citrate synthase subfamilies, as tca_cycle asserts on the base family. PrpC (SF25) is included because it retains citrate synthase activity as a minor component; for SF25 the term is secondary and non-core, and 2-methylcitrate synthase is the physiological activity.
mitochondrial_citrate_synthase_activity eukaryotic type I citrate synthase family
PANTHER:PTHR11739:SF29
Family 		citrate synthase activity
GO:0036440 		Family Supported
Family review supports GO:0036440 for PANTHER:PTHR11739:SF29. Citrate synthase subfamilies, as tca_cycle asserts on the base family. PrpC (SF25) is included because it retains citrate synthase activity as a minor component; for SF25 the term is secondary and non-core, and 2-methylcitrate synthase is the physiological activity.
mitochondrial_citrate_synthase_activity eukaryotic type I citrate synthase family
PANTHER:PTHR11739:SF27
Family 		citrate synthase activity
GO:0036440 		Family Supported
Family review supports GO:0036440 for PANTHER:PTHR11739:SF27. Citrate synthase subfamilies, as tca_cycle asserts on the base family. PrpC (SF25) is included because it retains citrate synthase activity as a minor component; for SF25 the term is secondary and non-core, and 2-methylcitrate synthase is the physiological activity.
aconitate_hydratase_activity aconitate hydratase families (AcnA/mitochondrial-type and AcnB-type)
Family 		aconitate hydratase activity
GO:0003994 		Family Id Missing
The family has no identifier linking it to a curated family review.
isocitrate_dehydrogenase_nadp_activity bacterial NADP-dependent isocitrate dehydrogenase families (dimeric Icd and monomeric Idh)
Family 		isocitrate dehydrogenase (NADP+) activity
GO:0004450 		Family Id Missing
The family has no identifier linking it to a curated family review.
oxoglutarate_dehydrogenase_activity 2-oxoglutarate dehydrogenase E1 family (SucA/KGD1/OGDH)
PANTHER:PTHR23152:SF4
Family 		oxoglutarate dehydrogenase (succinyl-transferring) activity
GO:0004591 		Family Supported
Family review supports GO:0004591 for PANTHER:PTHR23152:SF4. OGDH E1 in SF4, SF7 and SF5, as tca_cycle asserts on the base family; accepted by SucA, KGD1 and kgd1.
oxoglutarate_dehydrogenase_activity 2-oxoglutarate dehydrogenase E1 family (SucA/KGD1/OGDH)
PANTHER:PTHR23152:SF7
Family 		oxoglutarate dehydrogenase (succinyl-transferring) activity
GO:0004591 		Family Supported
Family review supports GO:0004591 for PANTHER:PTHR23152:SF7. OGDH E1 in SF4, SF7 and SF5, as tca_cycle asserts on the base family; accepted by SucA, KGD1 and kgd1.
oxoglutarate_dehydrogenase_activity 2-oxoglutarate dehydrogenase E1 family (SucA/KGD1/OGDH)
PANTHER:PTHR23152:SF5
Family 		oxoglutarate dehydrogenase (succinyl-transferring) activity
GO:0004591 		Family Supported
Family review supports GO:0004591 for PANTHER:PTHR23152:SF5. OGDH E1 in SF4, SF7 and SF5, as tca_cycle asserts on the base family; accepted by SucA, KGD1 and kgd1.
dihydrolipoyl_succinyltransferase_activity 2-oxoglutarate dehydrogenase E2 family (SucB/KGD2/DLST)
PANTHER:PTHR43416:SF5
Family 		dihydrolipoyllysine-residue succinyltransferase activity
GO:0004149 		Family Supported
Family review supports GO:0004149 for PANTHER:PTHR43416:SF5. Asserted by tca_cycle; accepted by DLST, KGD2, kgd2 and bacterial SucB.
dihydrolipoyl_succinyltransferase_activity 2-oxoglutarate dehydrogenase E2 family (SucB/KGD2/DLST)
PANTHER:PTHR43416:SF18
Family 		dihydrolipoyllysine-residue succinyltransferase activity
GO:0004149 		Family Supported
Family review supports GO:0004149 for PANTHER:PTHR43416:SF18. Asserted by tca_cycle; accepted by DLST, KGD2, kgd2 and bacterial SucB.
dihydrolipoyl_succinyltransferase_activity 2-oxoglutarate dehydrogenase E2 family (SucB/KGD2/DLST)
PANTHER:PTHR43416:SF40
Family 		dihydrolipoyllysine-residue succinyltransferase activity
GO:0004149 		Family Supported
Family review supports GO:0004149 for PANTHER:PTHR43416:SF40. Asserted by tca_cycle; accepted by DLST, KGD2, kgd2 and bacterial SucB.
dihydrolipoyl_succinyltransferase_activity 2-oxoglutarate dehydrogenase E2 family (SucB/KGD2/DLST)
PANTHER:PTHR43416:SF41
Family 		dihydrolipoyllysine-residue succinyltransferase activity
GO:0004149 		Family Supported
Family review supports GO:0004149 for PANTHER:PTHR43416:SF41. Asserted by tca_cycle; accepted by DLST, KGD2, kgd2 and bacterial SucB.
dihydrolipoyl_dehydrogenase_activity dihydrolipoyl dehydrogenase E3 family (Lpd/LPD1/DLD)
PANTHER:PTHR22912:SF151
Family 		dihydrolipoyl dehydrogenase (NADH) activity
GO:0004148 		Family Supported
Family review supports GO:0004148 for PANTHER:PTHR22912:SF151. The E3 subfamilies, not the divergent SthA transhydrogenase. SF219 is included on the basis of its independently mapped AcoL representative, the native sequence-based E3 assignment in PMID:10368162 and the conserved catalytic architecture. This extends chemistry scope, not a requirement that all E3 paralogs serve the same physiological complexes. No new PAINT node is inferred.
dihydrolipoyl_dehydrogenase_activity dihydrolipoyl dehydrogenase E3 family (Lpd/LPD1/DLD)
PANTHER:PTHR22912:SF160
Family 		dihydrolipoyl dehydrogenase (NADH) activity
GO:0004148 		Family Supported
Family review supports GO:0004148 for PANTHER:PTHR22912:SF160. The E3 subfamilies, not the divergent SthA transhydrogenase. SF219 is included on the basis of its independently mapped AcoL representative, the native sequence-based E3 assignment in PMID:10368162 and the conserved catalytic architecture. This extends chemistry scope, not a requirement that all E3 paralogs serve the same physiological complexes. No new PAINT node is inferred.
dihydrolipoyl_dehydrogenase_activity dihydrolipoyl dehydrogenase E3 family (Lpd/LPD1/DLD)
PANTHER:PTHR22912:SF224
Family 		dihydrolipoyl dehydrogenase (NADH) activity
GO:0004148 		Family Supported
Family review supports GO:0004148 for PANTHER:PTHR22912:SF224. The E3 subfamilies, not the divergent SthA transhydrogenase. SF219 is included on the basis of its independently mapped AcoL representative, the native sequence-based E3 assignment in PMID:10368162 and the conserved catalytic architecture. This extends chemistry scope, not a requirement that all E3 paralogs serve the same physiological complexes. No new PAINT node is inferred.
dihydrolipoyl_dehydrogenase_activity dihydrolipoyl dehydrogenase E3 family (Lpd/LPD1/DLD)
PANTHER:PTHR22912:SF217
Family 		dihydrolipoyl dehydrogenase (NADH) activity
GO:0004148 		Family Supported
Family review supports GO:0004148 for PANTHER:PTHR22912:SF217. The E3 subfamilies, not the divergent SthA transhydrogenase. SF219 is included on the basis of its independently mapped AcoL representative, the native sequence-based E3 assignment in PMID:10368162 and the conserved catalytic architecture. This extends chemistry scope, not a requirement that all E3 paralogs serve the same physiological complexes. No new PAINT node is inferred.
dihydrolipoyl_dehydrogenase_activity dihydrolipoyl dehydrogenase E3 family (Lpd/LPD1/DLD)
PANTHER:PTHR22912:SF220
Family 		dihydrolipoyl dehydrogenase (NADH) activity
GO:0004148 		Family Supported
Family review supports GO:0004148 for PANTHER:PTHR22912:SF220. The E3 subfamilies, not the divergent SthA transhydrogenase. SF219 is included on the basis of its independently mapped AcoL representative, the native sequence-based E3 assignment in PMID:10368162 and the conserved catalytic architecture. This extends chemistry scope, not a requirement that all E3 paralogs serve the same physiological complexes. No new PAINT node is inferred.
dihydrolipoyl_dehydrogenase_activity dihydrolipoyl dehydrogenase E3 family (Lpd/LPD1/DLD)
PANTHER:PTHR22912:SF223
Family 		dihydrolipoyl dehydrogenase (NADH) activity
GO:0004148 		Family Supported
Family review supports GO:0004148 for PANTHER:PTHR22912:SF223. The E3 subfamilies, not the divergent SthA transhydrogenase. SF219 is included on the basis of its independently mapped AcoL representative, the native sequence-based E3 assignment in PMID:10368162 and the conserved catalytic architecture. This extends chemistry scope, not a requirement that all E3 paralogs serve the same physiological complexes. No new PAINT node is inferred.
dihydrolipoyl_dehydrogenase_activity dihydrolipoyl dehydrogenase E3 family (Lpd/LPD1/DLD)
PANTHER:PTHR22912:SF207
Family 		dihydrolipoyl dehydrogenase (NADH) activity
GO:0004148 		Family Supported
Family review supports GO:0004148 for PANTHER:PTHR22912:SF207. The E3 subfamilies, not the divergent SthA transhydrogenase. SF219 is included on the basis of its independently mapped AcoL representative, the native sequence-based E3 assignment in PMID:10368162 and the conserved catalytic architecture. This extends chemistry scope, not a requirement that all E3 paralogs serve the same physiological complexes. No new PAINT node is inferred.
kgd4_adaptor_activity Kgd4/MRPS36 adaptor family
PANTHER:PTHR31601
Family 		protein-macromolecule adaptor activity
GO:0030674 		Family Supported
Family review supports GO:0030674 FAMILY_WIDE. Asserted by tca_cycle; accepted by KGD4.
sdha_flavoprotein_unit succinate dehydrogenase flavoprotein subunit family
PANTHER:PTHR11632:SF51
Family 		succinate dehydrogenase activity
GO:0000104 		Family Supported
Family review supports GO:0000104 for PANTHER:PTHR11632:SF51. Complex II flavoproteins (SF51, SF53, SF72), as tca_cycle and mitochondrial_complex_ii assert on the base family, which also takes in the fumarate reductases. Desulfovibrio AprA in SF51 is a member exception.
sdha_flavoprotein_unit succinate dehydrogenase flavoprotein subunit family
PANTHER:PTHR11632:SF53
Family 		succinate dehydrogenase activity
GO:0000104 		Family Supported
Family review supports GO:0000104 for PANTHER:PTHR11632:SF53. Complex II flavoproteins (SF51, SF53, SF72), as tca_cycle and mitochondrial_complex_ii assert on the base family, which also takes in the fumarate reductases. Desulfovibrio AprA in SF51 is a member exception.
sdha_flavoprotein_unit succinate dehydrogenase flavoprotein subunit family
PANTHER:PTHR11632:SF72
Family 		succinate dehydrogenase activity
GO:0000104 		Family Supported
Family review supports GO:0000104 for PANTHER:PTHR11632:SF72. Complex II flavoproteins (SF51, SF53, SF72), as tca_cycle and mitochondrial_complex_ii assert on the base family, which also takes in the fumarate reductases. Desulfovibrio AprA in SF51 is a member exception.
sdhb_iron_sulfur_unit succinate dehydrogenase iron-sulfur subunit family
PANTHER:PTHR11921
Family 		electron transfer activity
GO:0009055 		Family Supported
Family review supports GO:0009055 FAMILY_WIDE. Asserted by tca_cycle and mitochondrial_complex_ii; accepted by SDH2, SDHB and P. putida SdhB.
fumarate_hydratase_activity class-I and class-II fumarate hydratase families
Family 		fumarate hydratase activity
GO:0004333 		Family Id Missing
The family has no identifier linking it to a curated family review.
malate_dehydrogenase_nad_activity NAD-dependent malate dehydrogenase families (bacterial Mdh and mitochondrial MDH)
Family 		L-malate dehydrogenase (NAD+) activity
GO:0030060 		Family Id Missing
The family has no identifier linking it to a curated family review.
malate_dehydrogenase_quinone_activity bacterial malate:quinone oxidoreductase family
Family 		L-malate dehydrogenase (quinone) activity
GO:0008924 		Family Id Missing
The family has no identifier linking it to a curated family review.

Gene-review completeness (61/61 grounded genes reviewed)

59 complete review(s) · 42 with deep research · 0 missing review · 19 reviewed but lacking deep research

Gene Review Complete Deep research
acnA-I Q88L24 ✓ ✓ ✓
acnB Q88KF1 ✓ ✓ ✓
ACO1 P19414 ✓ ✓ ✓
CIT1 P00890 ✓ ✓ ✓
cit1 Q10306 ✓ ✓ ✗
CIT3 P43635 ✓ ✓ ✓
dld1 O00087 ✓ ✓ ✗
fum1 O94552 ✓ ✓ ✗
FUM1 P08417 ✓ ✓ ✓
fumC Q88M20 ✓ ✓ ✓
fumC-I Q88PA6 ✓ ✓ ✓
gltA Q88FA4 ✓ ✓ ✓
icd Q88FS2 ✓ ✓ ✓
idh Q88FS1 ✓ ✓ ✓
idh1 O13696 ✓ ✓ ✗
IDH1 P28834 ✓ ✓ ✓
IDH2 P28241 ✓ ✓ ✓
idh2 Q9USP8 ✓ ✓ ✗
kgd1 O74378 ✓ ✓ ✗
KGD1 P20967 ✓ ✓ ✓
kgd2 O94681 ✓ ✓ ✗
KGD2 P19262 ✓ ✓ ✓
kgd4 G2TRP3 ✓ ✓ ✗
KGD4 P19955 ✓ ✓ ✓
lpd P0A9P0 ✓ ✓ ✗
LPD1 P09624 ✓ ✓ ✓
lpdG Q88FB1 ✓ ✓ ✓
LSC1 P53598 ✓ ✓ ✓
LSC2 P53312 ✓ ✓ ✓
mdh Q88Q44 ✓ ✓ ✓
MDH1 P17505 ✓ ✓ ✓
mdh1 Q9Y7R8 ✓ ✓ ✗
mqo1 Q88PU7 ✓ ✓ ✓
mqo2 Q88NF9 ✓ ✓ ✓
mqo3 Q88IS4 ✓ ✓ ✓
PP_0897 Q88PF3 ✓ ✓ ✓
SDH1 Q00711 ✓ ✓ ✓
sdh1 Q9UTJ7 ✓ ✓ ✗
SDH2 P21801 ✓ ✓ ✓
sdh2 P21911 ✓ ✓ ✗
sdh3 O74882 ✓ ✓ ✗
SDH3 P33421 ✓ ✓ ✓
SDH4 P37298 ✓ ✓ ✓
sdh4 Q9P7X0 ✓ ✓ ✗
sdhA Q88FA7 ✓ ✓ ✓
sdhB Q88FA8 ✓ ✓ ✓
sdhC Q88FA5 ✓ ✓ ✓
sdhD Q88FA6 ✓ ✓ ✓
SPAC16E8.17c O13750 ✓ ✓ ✗
SPAC24C9.06c O13966 ✓ ✓ ✗
SPCC1620.08 O94415 ✓ ✓ ✗
sucA P0AFG3 ✓ ✓ ✗
sucA Q88FA9 ✓ ✓ ✓
sucB P0AFG6 ✓ ✓ ✗
sucB Q88FB0 ✓ ✓ ✓
sucC P0A836 ✓ ✓ ✓
sucC Q88FB2 ✓ ✓ ✓
sucD P0AGE9 ✓ ✓ ✓
sucD Q88FB3 ✓ ✓ ✓
SUCLA2 Q9P2R7 ✓ 54/55 ✓
SUCLG1 P53597 ✓ 34/35 ✓

Details

Tricarboxylic acid cycleMetabolic Pathwaytca_cycle
tricarboxylic acid cycleGO:0006099

Connections

Citrate.
Isocitrate.
2-Oxoglutarate.
Succinyl-CoA.
Succinate.
Fumarate.
(S)-Malate.
Oxaloacetate closes the cycle.
Part 1: acetyl-CoA entry
Citrate synthaseReactioncitrate_synthase_step

Acetyl-CoA + oxaloacetate + H2O -> citrate + CoA. Two non-orthologous citrate synthase families implement the step.

Variant set: Citrate synthase family variants by enzyme family / lineage (One Or More)
Type II (hexameric) bacterial citrate synthaseReactiontype_ii_citrate_synthase_variant

Annotons

Type II citrate synthase
citrate_synthase_activity
Participant: Family: bacterial type II citrate synthase family (GltA)
Family:
bacterial type II citrate synthase family (GltA)PANTHER:PTHR42871
Representative Members: gltA (Pseudomonas putida KT2440)UniProtKB:Q88FA4

Function

citrate synthase activityGO:0036440
Substrates: acetyl-CoA oxaloacetate H2O
Products: citrate CoA

Condenses acetyl-CoA and oxaloacetate to form citrate, the committed entry step of the cycle, in Gram-negative bacteria.

Type I (dimeric) mitochondrial citrate synthaseReactiontype_i_mitochondrial_citrate_synthase_variant

Annotons

Mitochondrial citrate synthase
mitochondrial_citrate_synthase_activity
Participant: Family: eukaryotic type I citrate synthase family
Family:
eukaryotic type I citrate synthase family
Representative Members: CIT1 (Saccharomyces cerevisiae)UniProtKB:P00890 CIT3 (Saccharomyces cerevisiae)UniProtKB:P43635 cit1 (Schizosaccharomyces pombe)UniProtKB:Q10306

Function

citrate synthase activityGO:0036440
Substrates: acetyl-CoA oxaloacetate H2O
Products: citrate CoA

Locations

mitochondrial matrixGO:0005759

Mitochondrial matrix citrate synthase that condenses acetyl-CoA from pyruvate dehydrogenase or fatty-acid oxidation with oxaloacetate. The peroxisomal paralog of the same family (yeast CIT2) belongs to the glyoxylate cycle.

Part 2: citrate to isocitrate
Aconitate hydrataseReactionaconitate_hydratase_step

Annotons

Aconitase
aconitate_hydratase_activity
Participant: Family: aconitate hydratase families (AcnA/mitochondrial-type and AcnB-type)
Family:
aconitate hydratase families (AcnA/mitochondrial-type and AcnB-type)
Representative Members: acnA-I (Pseudomonas putida KT2440)UniProtKB:Q88L24 acnB (Pseudomonas putida KT2440)UniProtKB:Q88KF1 ACO1 (Saccharomyces cerevisiae)UniProtKB:P19414 aco1 (Schizosaccharomyces pombe)UniProtKB:O13966

Function

aconitate hydratase activityGO:0003994
Substrates: citrate
Products: isocitrate

Reversibly isomerizes citrate to isocitrate through cis-aconitate. Yeast ACO2 and S. pombe aco2 are aconitase-family homocitrate dehydratases of lysine biosynthesis, not TCA-cycle aconitases.

Part 3: isocitrate oxidation
Isocitrate dehydrogenaseReactionisocitrate_dehydrogenase_step

Oxidative decarboxylation of isocitrate to 2-oxoglutarate, with NADP+ in many bacteria and with NAD+ in eukaryotic mitochondria.

Variant set: Isocitrate dehydrogenase cofactor variants by cofactor specificity / lineage (One Or More)
Bacterial NADP-dependent isocitrate dehydrogenaseReactionnadp_isocitrate_dehydrogenase_variant

Annotons

NADP-dependent isocitrate dehydrogenase
isocitrate_dehydrogenase_nadp_activity
Participant: Family: bacterial NADP-dependent isocitrate dehydrogenase families (dimeric Icd and monomeric Idh)
Family:
bacterial NADP-dependent isocitrate dehydrogenase families (dimeric Icd and monomeric Idh)
Representative Members: icd (Pseudomonas putida KT2440)UniProtKB:Q88FS2 idh (Pseudomonas putida KT2440)UniProtKB:Q88FS1

Function

isocitrate dehydrogenase (NADP+) activityGO:0004450
Substrates: isocitrate NADP+
Products: 2-oxoglutarate CO2 NADPH

Oxidatively decarboxylates isocitrate to 2-oxoglutarate while reducing NADP+ in many bacteria.

Mitochondrial NAD-dependent isocitrate dehydrogenaseProtein Complexnad_isocitrate_dehydrogenase_variant

Annotons

NAD-dependent isocitrate dehydrogenase (IDH1/IDH2 hetero-octamer)
isocitrate_dehydrogenase_nad_activity
Participant: Protein Complex: mitochondrial NAD-dependent isocitrate dehydrogenase complex
Protein Complex:
mitochondrial NAD-dependent isocitrate dehydrogenase complex Allosterically AMP-activated hetero-octamer of regulatory and catalytic subunits (PMID:8369302).
Active units:
IDH2 catalytic subunit
Participant: Family: NAD-IDH catalytic subunit family
Family:
NAD-IDH catalytic subunit familyPANTHER:PTHR11835
Representative Members: IDH2 (Saccharomyces cerevisiae)UniProtKB:P28241 idh2 (Schizosaccharomyces pombe)UniProtKB:Q9USP8
Role: Catalytic subunit carrying the isocitrate-binding active site.
IDH1 regulatory subunit
Participant: Family: NAD-IDH regulatory subunit family
Family:
NAD-IDH regulatory subunit familyPANTHER:PTHR11835
Representative Members: IDH1 (Saccharomyces cerevisiae)UniProtKB:P28834 idh1 (Schizosaccharomyces pombe)UniProtKB:O13696
Role: Regulatory subunit mediating AMP activation and cooperativity; required for activity.

Function

isocitrate dehydrogenase (NAD+) activityGO:0004449
Substrates: isocitrate NAD+
Products: 2-oxoglutarate CO2 NADH

Locations

mitochondrial matrixGO:0005759

The TCA-cycle isocitrate dehydrogenase of eukaryotic mitochondria; both subunits are required for activity (PMID:1939242, PMID:1644826) and the enzyme is needed for respiration with citrate, whereas the mitochondrial NADP-IDH is not (PMID:8099357).

Part 4: 2-oxoglutarate oxidation
2-oxoglutarate dehydrogenase complexMetabolic Pathwayoxoglutarate_dehydrogenase_complex_step

Multienzyme oxidative decarboxylation of 2-oxoglutarate to succinyl-CoA by E1, E2, and E3 components; in fungi and animals an additional adaptor subunit (Kgd4/MRPS36) tethers E3 to the E1-E2 core.

Part 1: E1 decarboxylation
2-oxoglutarate dehydrogenase E1Reactionoxoglutarate_dehydrogenase_e1_step

Annotons

2-oxoglutarate dehydrogenase
oxoglutarate_dehydrogenase_activity
Participant: Family: 2-oxoglutarate dehydrogenase E1 family (SucA/KGD1/OGDH)
Family:
2-oxoglutarate dehydrogenase E1 family (SucA/KGD1/OGDH)
Representative Members: sucA (Pseudomonas putida KT2440)UniProtKB:Q88FA9 sucA (Escherichia coli K-12)UniProtKB:P0AFG3 KGD1 (Saccharomyces cerevisiae)UniProtKB:P20967 kgd1 (Schizosaccharomyces pombe)UniProtKB:O74378

Function

oxoglutarate dehydrogenase (succinyl-transferring) activityGO:0004591
Substrates: 2-oxoglutarate
Products: succinyl-dihydrolipoamide
Part 2: E2 succinyltransferase
Dihydrolipoyllysine-residue succinyltransferaseReactiondihydrolipoyl_succinyltransferase_step

Annotons

Dihydrolipoyllysine-residue succinyltransferase
dihydrolipoyl_succinyltransferase_activity
Participant: Family: 2-oxoglutarate dehydrogenase E2 family (SucB/KGD2/DLST)
Family:
2-oxoglutarate dehydrogenase E2 family (SucB/KGD2/DLST)
Representative Members: sucB (Pseudomonas putida KT2440)UniProtKB:Q88FB0 sucB (Escherichia coli K-12)UniProtKB:P0AFG6 KGD2 (Saccharomyces cerevisiae)UniProtKB:P19262 kgd2 (Schizosaccharomyces pombe)UniProtKB:O94681

Function

dihydrolipoyllysine-residue succinyltransferase activityGO:0004149
Substrates: succinyl-dihydrolipoamide CoA
Products: succinyl-CoA
Part 3: E3 lipoamide dehydrogenase
Dihydrolipoyl dehydrogenaseReactiondihydrolipoyl_dehydrogenase_step

Annotons

Dihydrolipoyl dehydrogenase
dihydrolipoyl_dehydrogenase_activity
Participant: Family: dihydrolipoyl dehydrogenase E3 family (Lpd/LPD1/DLD)
Family:
dihydrolipoyl dehydrogenase E3 family (Lpd/LPD1/DLD)
Representative Members: lpdG (Pseudomonas putida KT2440)UniProtKB:Q88FB1 lpd (Escherichia coli K-12)UniProtKB:P0A9P0 LPD1 (Saccharomyces cerevisiae)UniProtKB:P09624 dld1 (Schizosaccharomyces pombe)UniProtKB:O00087

Function

dihydrolipoyl dehydrogenase (NADH) activityGO:0004148
Substrates: dihydrolipoamide NAD+
Products: lipoamide NADH
Part 4: E3-recruiting adaptor (fungi and animals) (optional)
Kgd4 E3-recruiting adaptorProtein Complexoxoglutarate_dehydrogenase_e3_adaptor_step

Annotons

Kgd4/MRPS36 adaptor tethering E3 to the E1-E2 core
kgd4_adaptor_activity
Participant: Family: Kgd4/MRPS36 adaptor family
Family:
Kgd4/MRPS36 adaptor familyPANTHER:PTHR31601
Representative Members: KGD4 / YMR31 (Saccharomyces cerevisiae)UniProtKB:P19955 kgd4 (Schizosaccharomyces pombe)UniProtKB:G2TRP3

Function

protein-macromolecule adaptor activityGO:0030674

Locations

mitochondrial matrixGO:0005759

Non-catalytic subunit of the eukaryotic 2-oxoglutarate dehydrogenase complex, formerly assigned to the mitoribosome, that recruits E3 to the E1-E2 core (PMID:25165143). Absent from bacterial complexes.

Part 5: succinyl-CoA to succinate
Succinate-CoA ligaseReactionsuccinate_coa_ligase_step

Annotons

ADP-forming succinate-CoA ligase
succinate_coa_ligase_adp_activity
Participant: Protein Complex: heteromeric succinate-CoA ligase complex (SucCD / Lsc1-Lsc2)
Protein Complex:
heteromeric succinate-CoA ligase complex (SucCD / Lsc1-Lsc2)GO:0009361
Active units:
Beta subunit (SucC / LSC2)
Participant: Family: succinyl-CoA ligase beta subunit family
Family:
succinyl-CoA ligase beta subunit familyPANTHER:PTHR11815
Representative Members: sucC (Pseudomonas putida KT2440)UniProtKB:Q88FB2 LSC2 (Saccharomyces cerevisiae)UniProtKB:P53312 lsc2 (Schizosaccharomyces pombe)UniProtKB:O94415 SUCLA2 (Homo sapiens)UniProtKB:Q9P2R7 sucC (Escherichia coli K-12)UniProtKB:P0A836
Role: Nucleotide-binding beta subunit of the heteromeric ligase.
Alpha subunit (SucD / LSC1)
Participant: Family: succinyl-CoA ligase alpha subunit family
Family:
succinyl-CoA ligase alpha subunit familyPANTHER:PTHR11117
Representative Members: sucD (Pseudomonas putida KT2440)UniProtKB:Q88FB3 LSC1 (Saccharomyces cerevisiae)UniProtKB:P53598 sca1 (Schizosaccharomyces pombe)UniProtKB:O13750 SUCLG1 (Homo sapiens)UniProtKB:P53597 sucD (Escherichia coli K-12)UniProtKB:P0AGE9
Role: CoA- and phosphate-handling alpha subunit of the heteromeric ligase.

Function

succinate-CoA ligase (ADP-forming) activityGO:0004775
Substrates: succinyl-CoA ADP phosphate
Products: succinate ATP CoA

Conserves thioester energy by substrate-level phosphorylation. The yeast enzyme is ATP-specific (PMID:9874242); some organisms, including animals, also have a GDP-forming isoform (GO:0004776) that shares the alpha subunit. In animal mitochondria the shared alpha subunit (SUCLG1) pairs with either the ATP-specific beta subunit SUCLA2 (this ADP-forming reaction; human SUCLA2 review, core function GO:0004775 (contributes_to) in GO:0009361, mitochondrial matrix) or the GTP-specific SUCLG2. Human SUCLG1 and SUCLG2 are both reviewed: SUCLG1 contributes to the ADP-forming and the GDP-forming enzyme, and SUCLG2 is GDP-forming (GO:0004776) and is not a member of this ADP-forming annoton. The bacterial enzymes listed here are not ATP-specific: the E. coli enzyme also forms GTP, with about a tenth of the efficiency it has with ATP, and the P. putida reviews treat the ADP-forming and GDP-forming activities as unranked (the P. aeruginosa enzyme forms both nucleotides; the P. putida enzyme has not been assayed) and name the generic complex GO:0042709. This annoton records only their ADP-forming activity.

Part 6: succinate oxidation
Succinate dehydrogenaseReactionsuccinate_dehydrogenase_step

Annotons

Succinate dehydrogenase (quinone)
succinate_dehydrogenase_quinone_activity
Participant: Protein Complex: succinate dehydrogenase (respiratory complex II; SdhABCD / SDH1-4)
Protein Complex:
succinate dehydrogenase (respiratory complex II; SdhABCD / SDH1-4)GO:0045273
Active units:
SdhA / SDH1 flavoprotein subunit
Participant: Family: succinate dehydrogenase flavoprotein subunit family
Family:
succinate dehydrogenase flavoprotein subunit family
Representative Members: sdhA (Pseudomonas putida KT2440)UniProtKB:Q88FA7 SDH1 (Saccharomyces cerevisiae)UniProtKB:Q00711 sdh1 (Schizosaccharomyces pombe)UniProtKB:Q9UTJ7
Role: Catalyzes succinate oxidation at the FAD-containing active site.
Function:
succinate dehydrogenase activityGO:0000104
SdhB / SDH2 iron-sulfur subunit
Participant: Family: succinate dehydrogenase iron-sulfur subunit family
Family:
succinate dehydrogenase iron-sulfur subunit familyPANTHER:PTHR11921
Representative Members: sdhB (Pseudomonas putida KT2440)UniProtKB:Q88FA8 SDH2 (Saccharomyces cerevisiae)UniProtKB:P21801 sdh2 (Schizosaccharomyces pombe)UniProtKB:P21911
Role: Relays electrons from the flavoprotein toward the membrane quinone site.
Function:
electron transfer activityGO:0009055
SdhC / SDH3 cytochrome b membrane subunit
Participant: Family: succinate dehydrogenase cytochrome b subunit family
Family:
succinate dehydrogenase cytochrome b subunit familyPANTHER:PTHR10978
Representative Members: sdhC (Pseudomonas putida KT2440)UniProtKB:Q88FA5 SDH3 (Saccharomyces cerevisiae)UniProtKB:P33421 sdh3 (Schizosaccharomyces pombe)UniProtKB:O74882
Role: Contributes the cytochrome-b membrane anchor and quinone-interaction domain.
SdhD / SDH4 membrane anchor subunit
Participant: Family: succinate dehydrogenase membrane anchor subunit (bacterial SdhD and eukaryotic SDH4 families)
Family:
succinate dehydrogenase membrane anchor subunit (bacterial SdhD and eukaryotic SDH4 families)
Representative Members: sdhD (Pseudomonas putida KT2440)UniProtKB:Q88FA6 SDH4 (Saccharomyces cerevisiae)UniProtKB:P37298 sdh4 (Schizosaccharomyces pombe)UniProtKB:Q9P7X0
Role: Completes the membrane anchor and contributes to quinone-linked electron transfer.

Function

succinate dehydrogenase (quinone) activityGO:0008177
Substrates: succinate quinone
Products: fumarate quinol

Locations

plasma membraneGO:0005886 mitochondrial inner membraneGO:0005743

Membrane-bound complex II links succinate oxidation in the TCA cycle to respiratory electron transfer through the quinone pool (menaquinone/ubiquinone in bacteria, ubiquinone in mitochondria).

Part 7: fumarate hydration
Fumarate hydrataseReactionfumarate_hydratase_step

Annotons

Fumarate hydratase
fumarate_hydratase_activity
Participant: Family: class-I and class-II fumarate hydratase families
Family:
class-I and class-II fumarate hydratase families
Representative Members: PP_0897 (Pseudomonas putida KT2440)UniProtKB:Q88PF3 fumC-I (Pseudomonas putida KT2440)UniProtKB:Q88PA6 fumC (Pseudomonas putida KT2440)UniProtKB:Q88M20 FUM1 (Saccharomyces cerevisiae)UniProtKB:P08417 fum1 (Schizosaccharomyces pombe)UniProtKB:O94552

Function

fumarate hydratase activityGO:0004333
Substrates: fumarate H2O
Products: (S)-malate
Part 8: malate oxidation
Malate to oxaloacetateMetabolic Pathwaymalate_to_oxaloacetate_step

Regeneration of oxaloacetate from malate. Organisms may use an NAD-dependent malate dehydrogenase, one or more malate:quinone oxidoreductases, or both; eukaryotic mitochondria use the NAD-dependent matrix enzyme.

Annotons

NAD-dependent L-malate dehydrogenase
malate_dehydrogenase_nad_activity
Participant: Family: NAD-dependent malate dehydrogenase families (bacterial Mdh and mitochondrial MDH)
Family:
NAD-dependent malate dehydrogenase families (bacterial Mdh and mitochondrial MDH)
Representative Members: mdh (Pseudomonas putida KT2440)UniProtKB:Q88Q44 MDH1 (Saccharomyces cerevisiae)UniProtKB:P17505 mdh1 (Schizosaccharomyces pombe)UniProtKB:Q9Y7R8

Function

L-malate dehydrogenase (NAD+) activityGO:0030060
Substrates: (S)-malate NAD+
Products: oxaloacetate NADH
L-malate dehydrogenase (quinone)
malate_dehydrogenase_quinone_activity
Participant: Family: bacterial malate:quinone oxidoreductase family
Family:
bacterial malate:quinone oxidoreductase family
Representative Members: mqo1 (Pseudomonas putida KT2440)UniProtKB:Q88PU7 mqo2 (Pseudomonas putida KT2440)UniProtKB:Q88NF9 mqo3 (Pseudomonas putida KT2440)UniProtKB:Q88IS4

Function

L-malate dehydrogenase (quinone) activityGO:0008924
Substrates: (S)-malate quinone
Products: oxaloacetate quinol