Arginine catabolism via arginase and ornithine aminotransferase

Arginase and ornithine aminotransferase route arginine through ornithine to glutamate 5-semialdehyde, which equilibrates spontaneously with pyrroline-5-carboxylate (P5C). This comparative module covers demonstrated budding- and fission-yeast, Arabidopsis and human enzymes, without asserting identical flux or compartmentation throughout Eukaryota. In budding yeast, cytosolic P5C reduction makes proline, which can enter mitochondrial proline oxidation and semialdehyde oxidation; anaerobic cultures instead retain proline as an endpoint. Mitochondrial ornithine aminotransferase and P5C dehydrogenase permit direct semialdehyde oxidation in the plant and animal implementations. The aminotransferase is reversible, and its intestinal biosynthetic direction is outside this catabolic boundary. Plant arginases belong to a distinct arginase/agmatinase family. Urea disposal, transmembrane substrate supply, arginine re-synthesis, polyamine synthesis and regulation remain adjoining pathways.

MODULE:arginine_catabolism_arginase_pathwayDRAFTCONCRETEMetabolic Pathwaymodules/arginine_catabolism_arginase_pathway.yaml
L-arginine catabolic processGO:0006527 L-ornithine catabolic processGO:0006593
YeastPathways:ARGDEG-YEAST-PWY
arginine degradation (aerobic) (S. cerevisiae, SGD YeastPathways)
YeastCyc lists ARGINASE-RXN (CAR1), ORNITHINE-GLU-AMINOTRANSFERASE-RXN (CAR2), spontaneous cyclization, PYRROLINECARBREDUCT-RXN (PRO3), RXN-14903 (PUT1) and RXN-14116 with no catalyst; PUT2 (P07275) was added for RXN-14116. The aerobic route is the proline-shuttle variant.
YeastPathways:ARG-PRO-PWY
L-arginine degradation VI (arginase 2 pathway) (S. cerevisiae, SGD YeastPathways)
YeastCyc lists CAR1, CAR2, spontaneous cyclization and PRO3, ending at proline; this is the anaerobic proline end-point variant. Gene assignments were retained.
GO:0006527
L-arginine catabolic process
Module-level process.
GO:0006593
L-ornithine catabolic process
The ornithine aminotransferase step onward is ornithine catabolism.
PMID:6094498
Nucleotide sequence of the Saccharomyces cerevisiae arginase gene (CAR1) and its transcription under various physiological conditions.
CAR1 encodes S. cerevisiae arginase.
PMID:7985419
Cloning and sequencing of Schizosaccharomyces pombe car1 gene encoding arginase. Expression of the arginine anabolic and catabolic genes in response to arginine and related metabolites.
S. pombe car1 encodes an arginase that complements a S. cerevisiae car1 mutant; its synthesis is induced by arginine.
PMID:26075619
Deletion of Genes Encoding Arginase Improves Use of "Heavy" Isotope-Labeled Arginine for Mass Spectrometry in Fission Yeast.
Fission-yeast car1/aru1 double deletion prevents virtually all measured isotope-arginine conversion. The authors propose an Arg3-dependent ornithine/citrulline/arginine re-synthesis route to explain isotope pre-peaks; the old claim that this yeast lacks the route is contradicted.
ornithine carbamoyl transferase Arg3 is part of the “arginine re-synthesis pathway”
PMID:3036506
Molecular characterization of transposable-element-associated mutations that lead to constitutive L-ornithine aminotransferase expression in Saccharomyces cerevisiae.
CAR2 (cargB) encodes ornithine aminotransferase, an inducible enzyme.
PMID:6997271
Proline: an essential intermediate in arginine degradation in Saccharomyces cerevisiae.
Budding-yeast mutants establish a proline intermediate between ornithine-derived P5C and mitochondrial glutamate formation under the studied conditions. This is not a demonstration in all fungi.
Put- mutants excreted proline when grown on arginine or ornithine as the sole nitrogen source.
PMID:7009582
Subcellular compartmentation in control of converging pathways for proline and arginine metabolism in Saccharomyces cerevisiae.
Fractionation separates budding-yeast cytoplasmic P5C reductase from particulate P5C dehydrogenase; the original study calls the latter presumably mitochondrial.
are physically separated in yeast cells.
PMID:387737
Genetics and physiology of proline utilization in Saccharomyces cerevisiae: enzyme induction by proline.
The arginine-degradative pathway intersects proline degradation at P5C, and arginine-derived P5C induces the Put enzymes through its conversion to proline.
PMID:25112878
Proline biosynthesis is required for endoplasmic reticulum stress tolerance in Saccharomyces cerevisiae.
Under the tested culture conditions, pro1 and pro2 nulls grow without added proline whereas pro3 nulls cannot, consistent with arginine catabolism supplying P5C to PRO3.
PMID:12620851
Improved anaerobic use of arginine by Saccharomyces cerevisiae.
Anaerobic budding yeast normally retains one arginine nitrogen in proline. Engineered pro3 ure2 cells expressing targeting-sequence-deleted PUT2 bypass this limitation; the experiment does not establish endogenous cytosolic PUT2.
assimilation of all four rather than just three of the nitrogen atoms in arginine.
PMID:18419821
Ornithine-delta-aminotransferase is essential for arginine catabolism but not for proline biosynthesis.
Arabidopsis mitochondrial OAT is necessary for use of supplied arginine or ornithine as nitrogen; loss of OAT does not impair stress-induced proline accumulation in the tested conditions. This supports a catabolic connection to mitochondrial P5CDH, not universal absence of ornithine-derived proline in all plants.
These findings demonstrated that oat mutants could not use Arg or Orn as nitrogen sources for growth.
PMID:12679340
Yeast epiarginase regulation, an enzyme-enzyme activity control: identification of residues of ornithine carbamoyltransferase and arginase responsible for enzyme catalytic and regulatory activities.
Arginase and OTCase form a one-to-one complex in the presence of ornithine and arginine, inhibiting OTCase while arginase remains active.
PMID:28272331
Ornithine Aminotransferase, an Important Glutamate-Metabolizing Enzyme at the Crossroads of Multiple Metabolic Pathways.
Comparative review distinguishes demonstrated cytosolic fungal OAT from mitochondrial plant and mammalian OAT. Mammalian intestinal OAT can support ornithine/arginine synthesis, so the catabolic direction is conditional, not a universal property of OAT expression.
with the notable exception of the intestine, where citrulline (Cit) or arginine (Arg) are end products.
PMID:41887919
Current Insight into Human Ornithine Aminotransferase: A Review.
Human OAT review corroborates reversible PLP chemistry and spontaneous GSA/P5C equilibration. Its broad fungal localization statement is limited here to the demonstrated exemplars and is not evidence that every fungus uses the budding-yeast proline detour.
The GSA undergoes spontaneous cyclization
PMID:26284079
Physiological implications of arginine metabolism in plants.
Plant arginine-metabolism review links mitochondrial arginine utilization to nitrogen remobilization and distinguishes it from plastid biosynthesis. Transporter roles are condition dependent; this review alone does not prove an obligatory carrier or universal flux through every downstream branch.
It is thus conceivable that arginine catabolism serves on the one hand to mobilize nitrogen storages
PMID:39952693
Biochemistry, pharmacology, and in vivo function of arginases.
Recent mammalian arginase review supports mitochondrial ARG2 as distinct from hepatic ARG1 and explicitly cautions that expression, localization and activity differ among humans, primates and rodents. Immune and vascular effects are context, outside this catalytic module.
there are significant differences in Arg1 and Arg2 expression, cellular localization, and activity in humans and primates as compared to rodents
PMID:29412048
Arginase: A Multifaceted Enzyme Important in Health and Disease.
Reviewed as background, with a specific cross-taxon passage rejected: the statement that most bacteria, plants and yeasts have one mitochondrial ARG2 cannot establish localization or copy number. Bacteria lack mitochondria, fission yeast has two demonstrated arginases, and Arabidopsis has two ARGAHs. Primary target evidence governs the module.
Most plants, bacteria, yeasts, and invertebrates have only one arginase isoform
PMID:1939179
Roles of metal ions in the maintenance of the tertiary and quaternary structure of arginase from Saccharomyces cerevisiae.
Purified S. cerevisiae CAR1 had a weakly bound catalytic Mn ion and a more tightly bound predominantly Zn structural site. Do not turn the binuclear-Mn architecture of other arginases into a universal metal-occupancy assertion.
binding of a weakly bound Mn2+ ion confers catalytic activity.
PMID:8898077
Molecular cloning of cDNA for nonhepatic mitochondrial arginase (arginase II) and comparison of its induction with nitric oxide synthase in a murine macrophage-like cell line.
Human ARG2 precursor was imported into isolated mitochondria and processed. The same paper studies induction in a murine macrophage cell line; that regulatory result is not a human-cell assay.
The arginase II precursor synthesized in vitro was imported into isolated mitochondria and proteolytically processed.
PMID:32754173
The Neighboring Subunit Is Engaged to Stabilize the Substrate in the Active Site of Plant Arginases.
Primary structures of Arabidopsis ARGAH1 and Medicago arginase show hexameric plant enzymes, Mn-containing active sites and intersubunit ornithine recognition. These support the distinct plant arginase/agmatinase family, not a universal oligomeric state for all arginases.
plant hexameric arginases engage a long loop from the neighboring subunit
PMID:35752016
Phosphatidic acid binds to and stimulates the activity of ARGAH2 from Arabidopsis.
Recombinant Arabidopsis ARGAH2 arginase activity and its stimulation by phosphatidic acid were measured directly; the plant family is included for arginine hydrolysis independently of its additional agmatinase activity.
PA binding to AtARGAH2 leads to the enhancement of arginase enzymatic activity in a dose dependent manner.
PMID:28716421
Dual functioning of plant arginases provides a third route for putrescine synthesis.
Arabidopsis ARGAHs also support an ADC-linked agmatinase route in heterologous complementation and purified-enzyme assays. Chloroplast localization was observed by transient expression in Nicotiana; dominant native stress flux was proposed, not directly measured. This alternative chemistry lies outside the ornithine route.
ARGAH genes in leaves of Nicotiana benthamiana, showed that these proteins are localized to the chloroplast.
PMID:28345116
Oligomeric State and Thermal Stability of Apo- and Holo- Human Ornithine δ-Aminotransferase.
Purified human OAT has a tetramer-dimer equilibrium; an engineered dimer retains catalytic features. A compulsory hexamer is not required for the module reaction.
the catalytic unit of hOAT is the dimer.
PMID:22516612
The three-dimensional structural basis of type II hyperprolinemia.
Human ALDH4A1 catalysis and mutant inactivation ground semialdehyde oxidation. Ligand-bound high-resolution structures in this paper are from mouse; species provenance is retained.
Mutation of Ser352 to Leu is shown to abolish catalytic activity and eliminate NAD(+) binding.
PMID:11532180
A nuclear gene encoding mitochondrial Delta-pyrroline-5-carboxylate dehydrogenase and its potential role in protection from proline toxicity.
Arabidopsis P5CDH was identified by complementation of yeast put2 and experimentally targeted to mitochondria. This establishes the plant catabolic enzyme without claiming Arabidopsis NAD-versus-NADP kinetics from another species.
Complementation of the Deltaput2 mutant allowed identification of the Arabidopsis P5CDH gene.
PMID:15548746
The role of [Delta]1-pyrroline-5-carboxylate dehydrogenase in proline degradation.
Native Arabidopsis p5cdh mutants lack detectable proline degradation and are hypersensitive to arginine and ornithine, supporting convergence on the P5C/GSA catabolic pool together with the OAT experiments.
p5cdh mutants were hypersensitive toward Pro and other molecules producing P5C, such as Arg and Orn.
PMID:20435771
Iron-dependent remodeling of fungal metabolic pathways associated with ferrichrome biosynthesis.
Fission-yeast arginases have distinguishable regulation: car1 is iron-repressed while car3 (the aru1 synonym) is constitutively expressed in the assayed conditions. Ornithine supply to siderophore synthesis is an alternative output, outside this module.
Although car3(+) was constitutively expressed, car1(+) transcription levels were repressed upon exposure to iron
PMID:32978391
Yeast homologs of human MCUR1 regulate mitochondrial proline metabolism.
Put6/Put7 regulate mitochondrial proline metabolism; this study still describes proline entry through an unknown transporter. A regulatory mutant phenotype does not identify either protein as the carrier.
Proline enters the mitochondria via an unknown transporter
PMID:3125423
Proline utilization in Saccharomyces cerevisiae: sequence, regulation, and mitochondrial localization of the PUT1 gene product.
PUT1 mitochondrial targeting and oxygen-regulated expression were tested. High expression in respiratory-deficient cells separates transcriptional regulation from the respiratory electron-transfer requirement of proline utilization.
PUT1 expression in a [rho-] strain grown either aerobically or anaerobically is as high
PMID:20450881
Purification and characterization of Put1p from Saccharomyces cerevisiae.
Purified budding-yeast Put1p directly oxidizes proline using ubiquinone-1 as electron acceptor. This supports the quinone-linked enzyme reaction without identifying molecular oxygen as the immediate acceptor or establishing purified fission-yeast kinetics.
Put1p also exhibited high activity using ubiquinone-1 (CoQ(1)) as an electron acceptor
PMID:3025596
Amino-terminal fragments of delta 1-pyrroline-5-carboxylate dehydrogenase direct beta-galactosidase to the mitochondrial matrix in Saccharomyces cerevisiae.
Native budding-yeast PUT2 was localized to the mitochondrial matrix by fractionation and substrate latency. Fusion-protein targeting further tested its import sequence; fission-yeast matrix assignment remains comparative.
was localized to the matrix compartment by a mitochondrial fractionation procedure.

The taxon envelope denotes characterized eukaryotic implementations, not universal presence or physiological equivalence. The full proline detour and anaerobic endpoint have direct budding-yeast evidence; fission-yeast homologs and arginine-to-proline conversion support comparative coverage but do not independently demonstrate every shuttle step. ARG2 is the mitochondrial human exemplar; hepatic ARG1 and the complete ureagenic cycle are outside this boundary. Plant ARGAH1/ARGAH2 belong to PTHR11358, separate from PTHR43782 fungal/animal arginases, and their agmatinase activity is not the activity selected here. Mitochondrial localization supports the catabolic implementation; transient Nicotiana chloroplast localization and context-dependent regulation are preserved in the individual reviews. Human OAT and ALDH4A1 biochemical evidence replaces citations to review YAML files. P5C/GSA equilibration is spontaneous, with the open-chain aldehyde used by P5CDH; it is not assigned to an invented enzyme. SGD imports put mitochondrial PUT1/PUT2 activities in cytosol; primary localization evidence governs this module. The PomBase GO:0000050 annotations are not rejected merely because S. pombe is not a mammalian ureotelic organism: PMID26075619 explicitly models Arg3-dependent arginine re-synthesis. Its isotope data and proposed detailed route are distinguished. Epiarginase inhibition of ARG3 is a regulatory edge outside the catalytic chain. The 2018 arginase review contains an overgeneralized localization/copy-number statement and is not used as authority for it. Native flux is not inferred from family labels alone; exact PANTHER names may reflect a different dominant activity, so selectors retain explicit required functions.

14Nodes
6Parts
3Variant Sets
7Variants
9Annotons
4Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:arginine_catabolism_arginase_pathway deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

19 gene-function check(s) reflected in core functions · 0 conflict(s) · 3 evidence or coverage gap(s) (28 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
arginase_activity CAR1 (Saccharomyces cerevisiae)
UniProtKB:P00812
Family Representative 		arginase activity
GO:0004053 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
arginase_activity car1 (Schizosaccharomyces pombe)
UniProtKB:P37818
Family Representative 		arginase activity
GO:0004053 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
arginase_activity aru1 (Schizosaccharomyces pombe)
UniProtKB:Q10066
Family Representative 		arginase activity
GO:0004053 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
arginase_activity ARG2 (Homo sapiens)
UniProtKB:P78540
Family Representative 		arginase activity
GO:0004053 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
plant_arginase_activity ARGAH1 (Arabidopsis thaliana)
UniProtKB:P46637
Family Representative 		arginase activity
GO:0004053 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
plant_arginase_activity ARGAH2 (Arabidopsis thaliana)
UniProtKB:Q9ZPF5
Family Representative 		arginase activity
GO:0004053 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
catabolic_oat_activity CAR2 (Saccharomyces cerevisiae)
UniProtKB:P07991
Family Representative 		L-ornithine transaminase activity
GO:0004587 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
catabolic_oat_activity car2 (Schizosaccharomyces pombe)
UniProtKB:Q9P7L5
Family Representative 		L-ornithine transaminase activity
GO:0004587 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
catabolic_oat_activity OAT (Homo sapiens)
UniProtKB:P04181
Family Representative 		L-ornithine transaminase activity
GO:0004587 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
catabolic_oat_activity DELTA-OAT (Arabidopsis thaliana)
UniProtKB:Q9FNK4
Family Representative 		L-ornithine transaminase activity
GO:0004587 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
shuttle_pycr_activity PRO3 (Saccharomyces cerevisiae)
UniProtKB:P32263
Family Representative 		pyrroline-5-carboxylate reductase activity
GO:0004735 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
shuttle_pycr_activity pro3 (Schizosaccharomyces pombe)
UniProtKB:Q9P7Y7
Family Representative 		pyrroline-5-carboxylate reductase activity
GO:0004735 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
shuttle_prodh_activity PUT1 (Saccharomyces cerevisiae)
UniProtKB:P09368
Family Representative 		proline dehydrogenase activity
GO:0004657 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
shuttle_prodh_activity put1 (Schizosaccharomyces pombe)
UniProtKB:O74524
Family Representative 		proline dehydrogenase activity
GO:0004657 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
shuttle_p5cdh_activity PUT2 (Saccharomyces cerevisiae)
UniProtKB:P07275
Family Representative 		L-glutamate gamma-semialdehyde dehydrogenase activity
GO:0003842 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
shuttle_p5cdh_activity put2 (Schizosaccharomyces pombe)
UniProtKB:O74766
Family Representative 		L-glutamate gamma-semialdehyde dehydrogenase activity
GO:0003842 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
endpoint_pycr_activity PRO3 (Saccharomyces cerevisiae)
UniProtKB:P32263
Family Representative 		pyrroline-5-carboxylate reductase activity
GO:0004735 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
direct_animal_p5cdh_activity ALDH4A1 (Homo sapiens)
UniProtKB:P30038
Family Representative 		L-glutamate gamma-semialdehyde dehydrogenase activity
GO:0003842 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
direct_plant_p5cdh_activity ALDH12A1 (Arabidopsis thaliana)
UniProtKB:Q8VZC3
Family Representative 		L-glutamate gamma-semialdehyde dehydrogenase activity
GO:0003842 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
arginase_activity arginase family
PANTHER:PTHR43782
Family 		arginase activity
GO:0004053 		Family Supported
Family review supports GO:0004053 FAMILY_WIDE. Shared by the vertebrate ARG1/ARG2, fungal and bacterial arginases. This is the term both the arginine catabolism and urea cycle modules require of the family. The one substrate-diverged member seen in the inventory, Streptomyces DcsB, is a secondary-metabolism enzyme outside any module.
plant_arginase_activity Plant arginase/agmatinase family, selected for arginine hydrolysis
PANTHER:PTHR11358
Family 		arginase activity
GO:0004053 		Family Function Unreviewed
The family review has no applicable adjudication supporting or excluding GO:0004053.
catabolic_oat_activity ornithine aminotransferase subfamily
PANTHER:PTHR11986:SF18
Family 		L-ornithine transaminase activity
GO:0004587 		Family Supported
Family review supports GO:0004587 for PANTHER:PTHR11986:SF18. Safe for the ornithine aminotransferase subfamily (SF18; human OAT is in SF118 in the PANTHER 19 HMM files). Not safe for the acetylornithine, succinylornithine, putrescine, 5-aminovalerate or 4-aminobutyrate transaminases elsewhere in the family. The arginine catabolism module selects SF18, and the proline metabolism module selects SF18 and SF118.
shuttle_pycr_activity pyrroline-5-carboxylate reductase family
PANTHER:PTHR11645
Family 		pyrroline-5-carboxylate reductase activity
GO:0004735 		Family Supported
Family review supports GO:0004735 FAMILY_WIDE. Shared by the characterized ProC, ProH/ProI/ProG, PRO3, pro3, plant P5CR and PYCR1-3 enzymes across SF0, SF6, SF61, SF49 and SF53. This is the term the arginine catabolism and proline metabolism modules require of the family, and both select the whole family, which is acceptable given the exceptions below.
shuttle_prodh_activity proline dehydrogenase family
PANTHER:PTHR13914
Family 		proline dehydrogenase activity
GO:0004657 		Family Supported
Family review supports GO:0004657 FAMILY_WIDE. Safe for SF0 and SF31. PRODH2 (SF29) is the exception and is handled by a PAINT IRD. Both modules (arginine catabolism and proline metabolism) select the whole family for this activity, which is acceptable with that exception.
shuttle_p5cdh_activity fungal mitochondrial P5C dehydrogenase family
PANTHER:PTHR42862
Family 		L-glutamate gamma-semialdehyde dehydrogenase activity
GO:0003842 		Family Supported
Family review supports GO:0003842 FAMILY_WIDE. Shared by the monofunctional fungal and Firmicute enzymes and the PutA P5CDH domain. This is the term the arginine catabolism module requires of the family for PUT2 and SPBC24C6.04. The Legionella AstD-named members were not verified.
endpoint_pycr_activity pyrroline-5-carboxylate reductase family
PANTHER:PTHR11645
Family 		pyrroline-5-carboxylate reductase activity
GO:0004735 		Family Supported
Family review supports GO:0004735 FAMILY_WIDE. Shared by the characterized ProC, ProH/ProI/ProG, PRO3, pro3, plant P5CR and PYCR1-3 enzymes across SF0, SF6, SF61, SF49 and SF53. This is the term the arginine catabolism and proline metabolism modules require of the family, and both select the whole family, which is acceptable given the exceptions below.
direct_animal_p5cdh_activity animal mitochondrial P5C dehydrogenase implementation
PANTHER:PTHR14516
Family 		L-glutamate gamma-semialdehyde dehydrogenase activity
GO:0003842 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR14516.
direct_plant_p5cdh_activity plant mitochondrial P5C dehydrogenase implementation
PANTHER:PTHR43521
Family 		L-glutamate gamma-semialdehyde dehydrogenase activity
GO:0003842 		Family Function Unreviewed
The family review has no applicable adjudication supporting or excluding GO:0003842.

Gene-review completeness (18/18 grounded genes reviewed)

11 complete review(s) · 5 with deep research · 0 missing review · 13 reviewed but lacking deep research

Gene Review Complete Deep research
ALDH12A1 Q8VZC3 ✓ 17/21 ✗
ALDH4A1 P30038 ✓ ✓ ✗
ARG2 P78540 ✓ 41/42 ✗
ARGAH1 P46637 ✓ 19/21 ✗
ARGAH2 Q9ZPF5 ✓ 24/28 ✗
aru1 Q10066 ✓ ✓ ✗
CAR1 P00812 ✓ ✓ ✓
car1 P37818 ✓ ✓ ✗
CAR2 P07991 ✓ ✓ ✓
car2 Q9P7L5 ✓ 9/10 ✗
DELTA-OAT Q9FNK4 ✓ 20/23 ✗
OAT P04181 ✓ ✓ ✗
PRO3 P32263 ✓ ✓ ✓
pro3 Q9P7Y7 ✓ ✓ ✗
put1 O74524 ✓ ✓ ✗
PUT1 P09368 ✓ ✓ ✓
put2 O74766 ✓ ✓ ✗
PUT2 P07275 ✓ 22/23 ✓

Details

Context
EukaryotaNCBITaxon:2759
Arginine catabolism via arginase and ornithine aminotransferaseMetabolic Pathwayarginine_catabolism_arginase_pathway
L-arginine catabolic processGO:0006527 L-ornithine catabolic processGO:0006593
Context
EukaryotaNCBITaxon:2759

Connections

PMID:6997271
Proline: an essential intermediate in arginine degradation in Saccharomyces cerevisiae.
Budding-yeast mutants establish a proline intermediate between ornithine-derived P5C and mitochondrial glutamate formation under the studied conditions. This is not a demonstration in all fungi.
Put- mutants excreted proline when grown on arginine or ornithine as the sole nitrogen source.
PMID:18419821
Ornithine-delta-aminotransferase is essential for arginine catabolism but not for proline biosynthesis.
Arabidopsis mitochondrial OAT is necessary for use of supplied arginine or ornithine as nitrogen; loss of OAT does not impair stress-induced proline accumulation in the tested conditions. This supports a catabolic connection to mitochondrial P5CDH, not universal absence of ornithine-derived proline in all plants.
These findings demonstrated that oat mutants could not use Arg or Orn as nitrogen sources for growth.
PMID:26075619
Deletion of Genes Encoding Arginase Improves Use of "Heavy" Isotope-Labeled Arginine for Mass Spectrometry in Fission Yeast.
Fission-yeast car1/aru1 double deletion prevents virtually all measured isotope-arginine conversion. The authors propose an Arg3-dependent ornithine/citrulline/arginine re-synthesis route to explain isotope pre-peaks; the old claim that this yeast lacks the route is contradicted.
ornithine carbamoyl transferase Arg3 is part of the “arginine re-synthesis pathway”
PMID:6997271
Proline: an essential intermediate in arginine degradation in Saccharomyces cerevisiae.
Budding-yeast mutants establish a proline intermediate between ornithine-derived P5C and mitochondrial glutamate formation under the studied conditions. This is not a demonstration in all fungi.
Put- mutants excreted proline when grown on arginine or ornithine as the sole nitrogen source.
PMID:18419821
Ornithine-delta-aminotransferase is essential for arginine catabolism but not for proline biosynthesis.
Arabidopsis mitochondrial OAT is necessary for use of supplied arginine or ornithine as nitrogen; loss of OAT does not impair stress-induced proline accumulation in the tested conditions. This supports a catabolic connection to mitochondrial P5CDH, not universal absence of ornithine-derived proline in all plants.
These findings demonstrated that oat mutants could not use Arg or Orn as nitrogen sources for growth.
PMID:15548746
The role of [Delta]1-pyrroline-5-carboxylate dehydrogenase in proline degradation.
Native Arabidopsis p5cdh mutants lack detectable proline degradation and are hypersensitive to arginine and ornithine, supporting convergence on the P5C/GSA catabolic pool together with the OAT experiments.
p5cdh mutants were hypersensitive toward Pro and other molecules producing P5C, such as Arg and Orn.
PMID:41887919
Current Insight into Human Ornithine Aminotransferase: A Review.
Human OAT review corroborates reversible PLP chemistry and spontaneous GSA/P5C equilibration. Its broad fungal localization statement is limited here to the demonstrated exemplars and is not evidence that every fungus uses the budding-yeast proline detour.
The GSA undergoes spontaneous cyclization
Part 1: hydrolysis of L-arginine
L-arginine to L-ornithine and ureaReactionarginase_step
Variant set: Distinct families implementing arginine hydrolysis by protein family (One Or More)
Fungal and animal arginase implementationReactionfungal_animal_arginase_step

Annotons

Arginase
arginase_activity
Participant: Family: arginase family
Family:
arginase familyPANTHER:PTHR43782
Representative Members: CAR1 (Saccharomyces cerevisiae)UniProtKB:P00812 car1 (Schizosaccharomyces pombe)UniProtKB:P37818 aru1 (Schizosaccharomyces pombe)UniProtKB:Q10066 ARG2 (Homo sapiens)UniProtKB:P78540
Required Function:
arginase activityGO:0004053

Function

arginase activityGO:0004053
Substrates: L-arginineCHEBI:32682 waterCHEBI:15377
Products: L-ornithineCHEBI:46911 ureaCHEBI:16199
Cofactors: Mn(2+)CHEBI:29035

Processes

L-arginine catabolic processGO:0006527

Hydrolyzes arginine to ornithine and urea; fungal exemplars are cytosolic and human ARG2 is mitochondrial. CAR1-mediated inhibition of ARG3 is separate regulatory context.

Plant arginase/agmatinase family implementationReactionplant_arginase_step

Annotons

Plant arginine hydrolase activity
plant_arginase_activity
Participant: Family: Plant arginase/agmatinase family, selected for arginine hydrolysis
Family:
Plant arginase/agmatinase family, selected for arginine hydrolysisPANTHER:PTHR11358
Representative Members: ARGAH1 (Arabidopsis thaliana)UniProtKB:P46637 ARGAH2 (Arabidopsis thaliana)UniProtKB:Q9ZPF5
Required Function:
arginase activityGO:0004053

Function

arginase activityGO:0004053
Substrates: L-arginineCHEBI:32682 waterCHEBI:15377
Products: L-ornithineCHEBI:46911 ureaCHEBI:16199
Cofactors: Mn(2+)CHEBI:29035

Processes

L-arginine catabolic processGO:0006527

Plant arginine hydrolysis supplies ornithine to catabolism. ARGAH agmatinase activity is a distinct reaction; relative native use and localization depend on biological context.

Part 2: transamination of L-ornithine to glutamate 5-semialdehyde
L-ornithine to L-glutamate 5-semialdehyde/P5CReactionornithine_transamination_step

Annotons

Ornithine aminotransferase
catabolic_oat_activity
Participant: Family: ornithine aminotransferase subfamily
Family:
ornithine aminotransferase subfamilyPANTHER:PTHR11986:SF18
Representative Members: CAR2 (Saccharomyces cerevisiae)UniProtKB:P07991 car2 (Schizosaccharomyces pombe)UniProtKB:Q9P7L5 OAT (Homo sapiens)UniProtKB:P04181 DELTA-OAT (Arabidopsis thaliana)UniProtKB:Q9FNK4
Required Function:
L-ornithine transaminase activityGO:0004587
The official PANTHER subfamily label says mitochondrial; the fungal members are cytosolic.

Function

L-ornithine transaminase activityGO:0004587
Substrates: L-ornithineCHEBI:46911 2-oxoglutarateCHEBI:16810
Products: L-glutamate 5-semialdehydeCHEBI:58066 L-glutamateCHEBI:29985
Cofactors: pyridoxal 5'-phosphateCHEBI:597326

Processes

L-arginine catabolic processGO:0006527 L-ornithine catabolic processGO:0006593

Transfers the ornithine delta-amino group to 2-oxoglutarate. Catabolic direction and compartment are implementation specific; mammalian intestinal biosynthetic OAT flux is outside this module.

Part 3: conversion of P5C to the pathway end product
P5C to L-glutamate or L-prolineMetabolic Pathwayp5c_disposal
Variant set: Route from P5C to the pathway end product by compartment and oxygen availability (One Or More)
Cytosolic proline formation and mitochondrial oxidation (demonstrated in budding yeast)Metabolic Pathwayproline_shuttle_route

The complete compartmental detour is demonstrated in S. cerevisiae. S. pombe supplies homologous enzymes and arginine-to-proline conversion evidence; assignment of the entire same shuttle remains comparative inference.

Connections

PMID:6997271
Proline: an essential intermediate in arginine degradation in Saccharomyces cerevisiae.
Budding-yeast mutants establish a proline intermediate between ornithine-derived P5C and mitochondrial glutamate formation under the studied conditions. This is not a demonstration in all fungi.
Put- mutants excreted proline when grown on arginine or ornithine as the sole nitrogen source.
PMID:7009582
Subcellular compartmentation in control of converging pathways for proline and arginine metabolism in Saccharomyces cerevisiae.
Fractionation separates budding-yeast cytoplasmic P5C reductase from particulate P5C dehydrogenase; the original study calls the latter presumably mitochondrial.
are physically separated in yeast cells.
PMID:32978391
Yeast homologs of human MCUR1 regulate mitochondrial proline metabolism.
Put6/Put7 regulate mitochondrial proline metabolism; this study still describes proline entry through an unknown transporter. A regulatory mutant phenotype does not identify either protein as the carrier.
Proline enters the mitochondria via an unknown transporter
PMID:6997271
Proline: an essential intermediate in arginine degradation in Saccharomyces cerevisiae.
Budding-yeast mutants establish a proline intermediate between ornithine-derived P5C and mitochondrial glutamate formation under the studied conditions. This is not a demonstration in all fungi.
Put- mutants excreted proline when grown on arginine or ornithine as the sole nitrogen source.
PMID:41887919
Current Insight into Human Ornithine Aminotransferase: A Review.
Human OAT review corroborates reversible PLP chemistry and spontaneous GSA/P5C equilibration. Its broad fungal localization statement is limited here to the demonstrated exemplars and is not evidence that every fungus uses the budding-yeast proline detour.
The GSA undergoes spontaneous cyclization
Part 1: cytosolic reduction of P5C to proline
P5C to L-proline (cytosol)Reactionshuttle_p5c_reduction

Annotons

Pyrroline-5-carboxylate reductase
shuttle_pycr_activity
Participant: Family: pyrroline-5-carboxylate reductase family
Family:
pyrroline-5-carboxylate reductase familyPANTHER:PTHR11645
Representative Members: PRO3 (Saccharomyces cerevisiae)UniProtKB:P32263 pro3 (Schizosaccharomyces pombe)UniProtKB:Q9P7Y7
Required Function:
pyrroline-5-carboxylate reductase activityGO:0004735

Function

pyrroline-5-carboxylate reductase activityGO:0004735
Substrates: (S)-1-pyrroline-5-carboxylateCHEBI:17388 NAD(P)H
Products: L-prolineCHEBI:60039 NAD(P)+

Processes

L-arginine catabolic processGO:0006527

Locations

cytosolGO:0005829

Converts cytosolic arginine-derived P5C into proline, the form that reaches the mitochondrial catabolic enzymes.

Part 2: mitochondrial oxidation of proline to P5C
L-proline to P5C (mitochondrion)Reactionshuttle_proline_oxidation

Annotons

Proline dehydrogenase
shuttle_prodh_activity
Participant: Family: proline dehydrogenase family
Family:
proline dehydrogenase familyPANTHER:PTHR13914
Representative Members: PUT1 (Saccharomyces cerevisiae)UniProtKB:P09368 put1 (Schizosaccharomyces pombe)UniProtKB:O74524
Required Function:
proline dehydrogenase activityGO:0004657

Function

proline dehydrogenase activityGO:0004657
Substrates: L-prolineCHEBI:60039 a quinoneCHEBI:132124
Products: (S)-1-pyrroline-5-carboxylateCHEBI:17388 a quinolCHEBI:24646
Cofactors: FADCHEBI:57692

Processes

L-arginine catabolic processGO:0006527 L-proline catabolic processGO:0006562

Locations

mitochondrionGO:0005739

Oxidation linked to mitochondrial electron transfer. Oxygen-dependent utilization is a property of the physiological route, not an assertion that molecular oxygen is the direct substrate or that PUT1 expression requires respiratory competence.

Part 3: mitochondrial oxidation of P5C to glutamate
P5C/glutamate 5-semialdehyde to L-glutamate (mitochondrial matrix)Reactionshuttle_p5c_oxidation

Annotons

P5C dehydrogenase
shuttle_p5cdh_activity
Participant: Family: fungal mitochondrial P5C dehydrogenase family
Family:
fungal mitochondrial P5C dehydrogenase familyPANTHER:PTHR42862
Representative Members: PUT2 (Saccharomyces cerevisiae)UniProtKB:P07275 put2 (Schizosaccharomyces pombe)UniProtKB:O74766
Required Function:
L-glutamate gamma-semialdehyde dehydrogenase activityGO:0003842

Function

L-glutamate gamma-semialdehyde dehydrogenase activityGO:0003842
Substrates: L-glutamate 5-semialdehydeCHEBI:58066 NAD+CHEBI:57540
Products: L-glutamateCHEBI:29985 NADHCHEBI:57945

Processes

L-arginine catabolic processGO:0006527 L-proline catabolic processGO:0006562

Locations

mitochondrial matrixGO:0005759

Completes conversion of arginine carbon to glutamate.

Proline endpoint under anaerobic budding-yeast growthReactionanaerobic_proline_endpoint_route

Under the tested anaerobic S. cerevisiae conditions, proline is not utilized and one arginine nitrogen remains in it. Engineered cytosolic PUT2 can bypass this limitation; this is not the native route and does not establish universal fungal behavior.

Annotons

Pyrroline-5-carboxylate reductase
endpoint_pycr_activity
Participant: Family: pyrroline-5-carboxylate reductase family
Family:
pyrroline-5-carboxylate reductase familyPANTHER:PTHR11645
Representative Members: PRO3 (Saccharomyces cerevisiae)UniProtKB:P32263
Required Function:
pyrroline-5-carboxylate reductase activityGO:0004735

Function

pyrroline-5-carboxylate reductase activityGO:0004735
Substrates: (S)-1-pyrroline-5-carboxylateCHEBI:17388 NAD(P)H
Products: L-prolineCHEBI:60039 NAD(P)+

Processes

L-arginine catabolic processGO:0006527

Locations

cytosolGO:0005829

Terminal step under anaerobiosis; the same reaction also lets pro1/pro2 mutants make proline from arginine (PMID:25112878).

Direct oxidation of OAT-derived P5C (animals, plants)Reactiondirect_mitochondrial_oxidation_route

Mitochondrial OAT and P5CDH provide compatible chemistry for direct semialdehyde oxidation. Arabidopsis OAT and P5CDH mutants support catabolic convergence; human enzyme chemistry supports the reaction pair without implying identical net flux in every tissue.

Variant set: Distinct mitochondrial P5CDH families by protein family (One Or More)
Direct animal P5C/GSA oxidationReactiondirect_animal_p5c_oxidation

Annotons

P5C dehydrogenase
direct_animal_p5cdh_activity
Participant: Family: animal mitochondrial P5C dehydrogenase implementation
Family:
animal mitochondrial P5C dehydrogenase implementationPANTHER:PTHR14516
Representative Members: ALDH4A1 (Homo sapiens)UniProtKB:P30038
Required Function:
L-glutamate gamma-semialdehyde dehydrogenase activityGO:0003842
Family membership is combined with the required P5C/GSA dehydrogenase activity; the official family label alone does not establish substrate specificity.

Function

L-glutamate gamma-semialdehyde dehydrogenase activityGO:0003842
Substrates: L-glutamate 5-semialdehydeCHEBI:58066 NAD+CHEBI:57540
Products: L-glutamateCHEBI:29985 NADHCHEBI:57945

Processes

L-arginine catabolic processGO:0006527

Locations

mitochondrial matrixGO:0005759

Oxidizes ornithine-derived semialdehyde to glutamate without passing through proline.

Direct plant P5C/GSA oxidationReactiondirect_plant_p5c_oxidation

Annotons

P5C dehydrogenase
direct_plant_p5cdh_activity
Participant: Family: plant mitochondrial P5C dehydrogenase implementation
Family:
plant mitochondrial P5C dehydrogenase implementationPANTHER:PTHR43521
Representative Members: ALDH12A1 (Arabidopsis thaliana)UniProtKB:Q8VZC3
Required Function:
L-glutamate gamma-semialdehyde dehydrogenase activityGO:0003842
Family membership is combined with the required P5C/GSA dehydrogenase activity; the official family label alone does not establish substrate specificity.

Function

L-glutamate gamma-semialdehyde dehydrogenase activityGO:0003842
Substrates: L-glutamate 5-semialdehydeCHEBI:58066 NAD+CHEBI:57540
Products: L-glutamateCHEBI:29985 NADHCHEBI:57945

Processes

L-arginine catabolic processGO:0006527

Locations

mitochondrionGO:0005739

Oxidizes ornithine-derived semialdehyde to glutamate without passing through proline.