ALDH5A1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004777 succinate-semialdehyde dehydrogenase (NAD+) activity	IBA GO_REF:0000033	ACCEPT	Summary: Conserved NAD+-dependent SSADH catalysis is supported by PAINT and direct human enzymology. Reason: The cached PAINT IBD at PANTHER:PTN008681047 places SSADH catalysis in the ancestral lineage inherited by human ALDH5A1. Recombinant human enzyme turns over succinic semialdehyde with NAD+ (PMID:16199352), independently supporting retention. Human experimental evidence among the descendants is valid grounding for the ancestral assertion. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008681047 SUPPORTS TRANSFER The cached PTHR43353 PAINT record contains this catalytic IBD; direct human NAD+-dependent turnover corroborates the inherited function. The complete historical tree/MSA was not reconstructed. Supporting Evidence: PMID:16199352 The succinic semialdehyde dehydrogenase gene (SSADH; EC 1.2.1.24) from human brain was cloned and overexpressed in Escherichia coli. PMID:16199352 The Michaelis constants K(m) for succinic semialdehyde and NAD(+) were 6.3 and 125 microM, respectively.
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: The PAINT mitochondrial assignment agrees with human SSADH compartment evidence. Reason: The cached mitochondrial IBD at PANTHER:PTN000192583 includes human and mouse experimental grounding. The human literature places SSADH-mediated oxidation in the mitochondrial matrix (PMID:19300440). Mitochondrion is an accurate compartment at the resolution of this ancestral assertion; the separate matrix annotation supplies finer localization. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000192583 SUPPORTS TRANSFER The cached PTHR43353 PAINT record contains this mitochondrial IBD, grounded in human P51649 and mouse MGI:MGI:2441982 evidence. Human matrix biochemistry independently supports retention. The complete historical tree/MSA was not reconstructed. Supporting Evidence: PMID:19300440 Succinic semialdehyde dehydrogenase (SSADH) is involved in the final degradation step of the inhibitory neurotransmitter gamma-aminobutyric acid by converting succinic semialdehyde to succinic acid in the mitochondrial matrix.
GO:0009450 GABA catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: ALDH5A1 executes the final catalytic step of GABA degradation. Reason: The GABA-catabolism IBD at PANTHER:PTN008681047 is consistent with the experimentally established human SSA-to-succinate reaction (PMID:12208142; PMID:16199352). ALDH5A1 directly performs a catabolic step, rather than merely changing GABA concentrations through an unrelated perturbation. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008681047 SUPPORTS TRANSFER The cached PTHR43353 PAINT record contains this GABA-catabolism IBD, with human and yeast experimental descendants. Target self-evidence is not circular. The complete historical tree/MSA was not reconstructed. Supporting Evidence: PMID:12208142 Mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase (ALDH5A1, SSADH) represents the last enzyme in the GABA catabolism and irreversibly oxidizes SSA to succinate. PMID:16199352 The Michaelis constants K(m) for succinic semialdehyde and NAD(+) were 6.3 and 125 microM, respectively.
GO:0004777 succinate-semialdehyde dehydrogenase (NAD+) activity	IEA GO_REF:0000120	ACCEPT	Summary: The combined electronic mapping identifies the established NAD+-dependent reaction. Reason: The cached UniProt catalytic statement maps RHEA:13217 and EC:1.2.1.24 to SSA oxidation with NAD+. Human recombinant kinetics provide independent experimental support (PMID:16199352). The uninspected ARBA predicate set remains unresolved in the source assessment. Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:13217 SUPPORTS TRANSFER The cached UniProt catalytic record explicitly assigns this identifier to SSA oxidation with NAD+; human kinetics corroborate the reaction. EC:1.2.1.24 SUPPORTS TRANSFER The cached UniProt catalytic record explicitly assigns this identifier to SSA oxidation with NAD+; human kinetics corroborate the reaction. ARBA:ARBA00096964 UNRESOLVED The rule identifier is preserved from GOA, but its predicate set was not inspected; independent biochemical support determines the annotation judgment. Supporting Evidence: file:human/ALDH5A1/ALDH5A1-uniprot.txt Reaction=succinate semialdehyde + NAD(+) + H2O = succinate + NADH + 2 CC H(+); Xref=Rhea:RHEA:13217, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30031, ChEBI:CHEBI:57540, ChEBI:CHEBI:57706, CC ChEBI:CHEBI:57945; EC=1.2.1.24; PMID:12208142 Mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase (ALDH5A1, SSADH) represents the last enzyme in the GABA catabolism and irreversibly oxidizes SSA to succinate. PMID:16199352 The Michaelis constants K(m) for succinic semialdehyde and NAD(+) were 6.3 and 125 microM, respectively.
GO:0005739 mitochondrion	IEA GO_REF:0000120	ACCEPT	Summary: Electronic ortholog and subcellular-location mappings support mitochondrial localization. Reason: The proximate sources are mouse Aldh5a1 Q8BWF0, its Ensembl protein and the UniProt mitochondrial compartment mapping. Mouse GO-CAM 68d5ebd600002976 traces mitochondrial localization to PMID:14651853; that cached abstract describes mouse organelle proteomics but does not expose the individual Aldh5a1 peptide record. Human matrix chemistry and localization evidence independently support the broad compartment (PMID:19300440). Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8BWF0 SUPPORTS TRANSFER Mouse Aldh5a1 is the ortholog; the cached mouse GO-CAM and MGI trace its mitochondrial evidence to PMID:14651853. The individual proteomic entry was not re-extracted. ensembl:ENSMUSP00000040591 SUPPORTS TRANSFER This is the mouse Aldh5a1 protein identifier associated with Q8BWF0, not an independently assayed protein. UniProtKB-SubCell:SL-0173 SUPPORTS TRANSFER The mitochondrial compartment mapping agrees with the cached human UniProt location and independent matrix literature. Supporting Evidence: PMID:19300440 Succinic semialdehyde dehydrogenase (SSADH) is involved in the final degradation step of the inhibitory neurotransmitter gamma-aminobutyric acid by converting succinic semialdehyde to succinic acid in the mitochondrial matrix.
GO:0009013 succinate-semialdehyde dehydrogenase [NAD(P)+] activity	IEA GO_REF:0000002	MODIFY	Summary: Refine the valid NAD(P)+ family activity to the established NAD+-dependent activity. Reason: GO:0009013 is a parent encompassing NAD+- and NADP+-dependent SSADH activities; its definition does not require an individual enzyme to use both cofactors. The human NAD+-dependent reaction is experimentally resolved (PMID:16199352), so GO:0004777 provides the appropriate specificity. This refinement does not assert that an NADP+ negative assay was read. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR010102 SUPPORTS TRANSFER The seeded InterPro mapping gives the broader SSADH cofactor class; positive human NAD+ kinetics justify narrowing. The current InterPro rule implementation was not independently reconstructed. Proposed replacements: succinate-semialdehyde dehydrogenase (NAD+) activity Supporting Evidence: PMID:16199352 The Michaelis constants K(m) for succinic semialdehyde and NAD(+) were 6.3 and 125 microM, respectively.
GO:0009450 GABA catabolic process	IEA GO_REF:0000120	ACCEPT	Summary: Electronic pathway mappings agree with direct GABA-catabolic participation. Reason: ALDH5A1 directly oxidizes the semialdehyde intermediate in GABA degradation (PMID:12208142). The InterPro and UniPathway source identifiers match that pathway-level assertion; it is supported by human chemistry independently of the uninspected current mapping predicates. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR010102 UNRESOLVED GOA records this SSADH-family mapping, but its current rule predicates were not inspected. Human catalytic evidence independently supports the pathway assertion. UniPathway:UPA00733 SUPPORTS TRANSFER The cached UniProt record links this identifier to 4-aminobutanoate degradation, consistent with the human SSA oxidation step. Supporting Evidence: PMID:12208142 Mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase (ALDH5A1, SSADH) represents the last enzyme in the GABA catabolism and irreversibly oxidizes SSA to succinate.
GO:0016491 oxidoreductase activity	IEA GO_REF:0000002	MODIFY	Summary: Refine generic oxidoreductase activity to human SSADH catalysis. Reason: The aldehyde-dehydrogenase domain mappings support an oxidoreductase class, while purified human SSADH establishes the substrate and NAD+ cofactor (PMID:16199352). GO:0004777 therefore expresses the measured function more precisely than GO:0016491; the broad redox activity is not biologically false. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR015590 UNRESOLVED This is a seeded InterPro domain mapping to a broad redox function. Current mapping predicates were not inspected; purified human SSADH supplies the independent, more specific reaction evidence. InterPro:IPR016160 UNRESOLVED This is a seeded InterPro domain mapping to a broad redox function. Current mapping predicates were not inspected; purified human SSADH supplies the independent, more specific reaction evidence. InterPro:IPR029510 UNRESOLVED This is a seeded InterPro domain mapping to a broad redox function. Current mapping predicates were not inspected; purified human SSADH supplies the independent, more specific reaction evidence. Proposed replacements: succinate-semialdehyde dehydrogenase (NAD+) activity Supporting Evidence: PMID:16199352 The succinic semialdehyde dehydrogenase gene (SSADH; EC 1.2.1.24) from human brain was cloned and overexpressed in Escherichia coli. PMID:16199352 The Michaelis constants K(m) for succinic semialdehyde and NAD(+) were 6.3 and 125 microM, respectively.
GO:0006540 GABA shunt	IMP PMID:15037717 Proton MR spectroscopy in succinic semialdehyde dehydrogenas...	ACCEPT	Summary: The patient MRS phenotype corroborates SSADH participation in the GABA shunt. Reason: PMID:15037717 measures elevated GABA and traces of GHB in a patient with SSADH deficiency; it is a metabolic case study, not an isolated-enzyme assay. Independent human enzymology establishes that ALDH5A1 performs the final SSA oxidation step described in GO:0006540 (PMID:12208142; PMID:16199352). Together these support a core pathway role. Supporting Evidence: PMID:15037717 A characteristic pattern with clearly elevated GABA levels and traces of GHB was found in both the white and the gray matter of the brain. PMID:12208142 Mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase (ALDH5A1, SSADH) represents the last enzyme in the GABA catabolism and irreversibly oxidizes SSA to succinate.
GO:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: Retain the curated immunofluorescence mitochondrial assignment. Reason: GO_REF:0000052 identifies the immunofluorescence curation method. The original antibody images were not re-scored, but the assignment agrees with independent human mitochondrial SSADH evidence (PMID:19300440). This compartment annotation is retained at its experimentally supplied resolution; it is not automatically refined to matrix from microscopy alone. Supporting Evidence: PMID:19300440 Succinic semialdehyde dehydrogenase (SSADH) is involved in the final degradation step of the inhibitory neurotransmitter gamma-aminobutyric acid by converting succinic semialdehyde to succinic acid in the mitochondrial matrix.
GO:0004777 succinate-semialdehyde dehydrogenase (NAD+) activity	EXP PMID:12208142 Structure of human succinic semialdehyde dehydrogenase gene:...	ACCEPT	Summary: Human gene and variant characterization supports NAD+-dependent SSADH activity. Reason: The cached PMID:12208142 abstract explicitly identifies ALDH5A1 as the mitochondrial NAD+-dependent SSA-oxidizing enzyme and reports natural variants affecting activity. Its alternative-polyadenylation experiments address transcript behavior; they do not establish identical catalytic properties for every protein isoform. Purified human enzymology independently confirms the annotated reaction. Supporting Evidence: PMID:12208142 Mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase (ALDH5A1, SSADH) represents the last enzyme in the GABA catabolism and irreversibly oxidizes SSA to succinate. PMID:16199352 The Michaelis constants K(m) for succinic semialdehyde and NAD(+) were 6.3 and 125 microM, respectively.
GO:0004777 succinate-semialdehyde dehydrogenase (NAD+) activity	EXP PMID:14635103 Mutational spectrum of the succinate semialdehyde dehydrogen...	ACCEPT	Summary: Human variant-expression experiments support SSADH catalysis. Reason: PMID:14635103 tests human variants in a mammalian expression system. The abstract reports that, with one exception, missense alleles judged causative reduced SSADH activity below 5% of normal; some other variants did not strongly affect activity. The measured activity supports the enzyme assignment without generalizing severe loss to every reported allele. Supporting Evidence: PMID:14635103 With one exception, the missense mutations we consider to be causative of SSADH deficiency reduced the SSADH activity to less than 5% of the normal activity in our in vitro expression system.
GO:0004777 succinate-semialdehyde dehydrogenase (NAD+) activity	EXP PMID:19300440 Redox-switch modulation of human SSADH by dynamic catalytic ...	ACCEPT	Summary: Human structures and NADH-formation assays establish SSADH activity and redox sensitivity. Reason: PMID:19300440 measures NAD+-dependent turnover and analyzes catalytic-loop mutants. The substrate complex contains SSA, and the cofactor-soaked structure resolves the ADP moiety of NAD+; these are not product-bound succinate or evidence that ADP is the catalytic cofactor. Oxidant/reductant experiments establish a redox-sensitive enzyme, while its quantitative regulation of endogenous neural GABA flux remains unresolved. Supporting Evidence: PMID:19300440 Succinic semialdehyde dehydrogenase (SSADH) is involved in the final degradation step of the inhibitory neurotransmitter gamma-aminobutyric acid by converting succinic semialdehyde to succinic acid in the mitochondrial matrix. PMID:16199352 The Michaelis constants K(m) for succinic semialdehyde and NAD(+) were 6.3 and 125 microM, respectively.
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: Retain the curated MitoCoP mitochondrial identification. Reason: PMID:34800366 combines complementary proteomic strategies to define a human mitochondrial inventory. Its main full text was inspected, but the ALDH5A1-specific supplementary entry was not independently extracted. The curated HTP assignment is retained because mitochondrial SSADH is independently established (PMID:19300440); the inventory-size statement alone is not treated as a gene-specific observation. Supporting Evidence: PMID:19300440 Succinic semialdehyde dehydrogenase (SSADH) is involved in the final degradation step of the inhibitory neurotransmitter gamma-aminobutyric acid by converting succinic semialdehyde to succinic acid in the mitochondrial matrix.
GO:0004777 succinate-semialdehyde dehydrogenase (NAD+) activity	IDA PMID:16199352 High-level expression and characterization of the recombinan...	ACCEPT	Summary: Purified recombinant human SSADH catalyzes NAD+-dependent semialdehyde oxidation. Reason: PMID:16199352 expresses the human brain cDNA in bacteria and reports active purified enzyme, substrate/cofactor Michaelis constants and NADH formation. This is direct positive evidence for the core molecular function. Supporting Evidence: PMID:16199352 The succinic semialdehyde dehydrogenase gene (SSADH; EC 1.2.1.24) from human brain was cloned and overexpressed in Escherichia coli. PMID:16199352 The Michaelis constants K(m) for succinic semialdehyde and NAD(+) were 6.3 and 125 microM, respectively.
GO:0042802 identical protein binding	IPI PMID:16199352 High-level expression and characterization of the recombinan...	ACCEPT	Summary: Homotetrameric self-association is an integral feature of the active enzyme. Reason: PMID:16199352 reports a purified active preparation consistent with a tetramer of identical subunits, corroborated by the human structural work in PMID:19300440. The interaction describes SSADH assembly rather than an unspecified binding partner, and is retained as a core molecular property within the integrated catalytic function. It does not create a separate signaling or adaptor function. Supporting Evidence: PMID:16199352 The purified SSADH appears to be a tetramer of identical subunits.
GO:0005739 mitochondrion	HDA PMID:20833797 Phosphoproteome analysis of functional mitochondria isolated...	ACCEPT	Summary: Retain the curated mitochondrial proteomics assignment with extraction limits stated. Reason: PMID:20833797 studies functional mitochondria isolated from human muscle. The local record contains abstract and Discussion sections but omits the relevant primary tables and much of the experimental text; the individual ALDH5A1 identification was not re-extracted. The HDA assignment is retained with curator deference and independent mitochondrial SSADH support (PMID:19300440), without inferring either contamination or a new submitochondrial location. Supporting Evidence: PMID:19300440 Succinic semialdehyde dehydrogenase (SSADH) is involved in the final degradation step of the inhibitory neurotransmitter gamma-aminobutyric acid by converting succinic semialdehyde to succinic acid in the mitochondrial matrix.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-888548	ACCEPT	Summary: The matrix-localized Reactome reaction agrees with the primary SSADH literature. Reason: The cached human Reactome event R-HSA-888548 describes tetrameric ALDH5A1 oxidizing SSA to succinate and cites the human biochemical and genetic studies. PMID:19300440 explicitly places this reaction in the mitochondrial matrix. These sources support the compartment of the core metabolic function. Supporting Evidence: Reactome:R-HSA-888548 Mitochondrial succinate semialdehyde dehydrogenase (ALDH5A1) tetramer catalyzes the reaction of succinate semialdehyde (SUCCSA), H2O, and NAD+ to form succinate (SUCCA) and NADH + 2 H+ (Kim et al. 2009). PMID:19300440 Succinic semialdehyde dehydrogenase (SSADH) is involved in the final degradation step of the inhibitory neurotransmitter gamma-aminobutyric acid by converting succinic semialdehyde to succinic acid in the mitochondrial matrix.
GO:0006105 succinate metabolic process	ISS GO_REF:0000024	ACCEPT	Summary: Succinate production is part of ALDH5A1's core catalytic work. Reason: ALDH5A1 directly produces succinate (PMID:12208142; PMID:16199352), satisfying the reactions-and-pathways scope of GO:0006105. GO:0006540 GABA shunt is also a child of this process. The mouse source is Q8BWF0: the historical MGI graph links the IMP assertion to J:125589/PMID:12065715. That paper's accessible abstract concerns treatment and metabolite phenotypes rather than a succinate-flux assay, so the human judgment is grounded in independently measured SSA oxidation, not an invented donor experiment. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8BWF0 SUPPORTS TRANSFER Mouse Aldh5a1. The MGI graph generated 2023-03-10 traces this IMP term to J:125589, resolved through MouseMine to PMID:12065715. Its abstract was read; full donor experiments were not recovered. Conserved enzyme chemistry and direct human SSA-to-succinate activity independently support transfer. Supporting Evidence: PMID:12208142 Mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase (ALDH5A1, SSADH) represents the last enzyme in the GABA catabolism and irreversibly oxidizes SSA to succinate. PMID:16199352 The Michaelis constants K(m) for succinic semialdehyde and NAD(+) were 6.3 and 125 microM, respectively.
GO:0006536 glutamate metabolic process	ISS GO_REF:0000024	ACCEPT	Summary: The GABA shunt is a glutamate-metabolic pathway in which ALDH5A1 catalyzes a step. Reason: ALDH5A1 catalyzes the SSA-to-succinate step that completes the glutamate-to-GABA-to-succinate shunt (PMID:12208142; PMID:16199352). GO:0006540 explicitly includes SSADH as the enzyme performing this final step and is an is_a child of GO:0006536. This is core catalytic participation in glutamate metabolism through an intermediate, without making glutamate an immediate enzyme substrate. The compact core describes this same work as GABA catabolism and need not repeat every broader pathway label. Mouse Q8BWF0 has an IMP source, J:128716/PMID:17854388, showing altered isotope labeling and amino-acid pools in deficient mice; those system-level effects are supporting context, not the basis for claiming direct human glutamate catalysis. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8BWF0 SUPPORTS TRANSFER Mouse Aldh5a1. The MGI graph generated 2023-03-10 and MouseMine resolve the source to PMID:17854388; primary PubMed/publisher abstracts describe mouse cortical tracer/metabolite experiments. Human GABA-shunt chemistry and the verified GO parent relationship independently support this broad process. Supporting Evidence: PMID:12208142 Mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase (ALDH5A1, SSADH) represents the last enzyme in the GABA catabolism and irreversibly oxidizes SSA to succinate.
GO:0004777 succinate-semialdehyde dehydrogenase (NAD+) activity	ISS PMID:7814412 Molecular cloning of the mature NAD(+)-dependent succinic se...	ACCEPT	Summary: Rat biochemical evidence and human conservation support the original ISS assignment. Reason: PMID:7814412 confirms the rat cDNA through bacterial enzyme activity and purified rat-brain protein sequence, and identifies human liver cDNA clones with high protein-sequence identity. The proximate source is rat P51650; bacterial activity in that study should not be relabeled as a human recombinant assay. Later direct human purification and kinetics (PMID:16199352) independently establish the transferred NAD+-dependent activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P51650 SUPPORTS TRANSFER Rat SSADH is the experimentally characterized donor in PMID:7814412; the same study compares human sequences. Later human recombinant activity validates the conserved reaction. Supporting Evidence: PMID:7814412 The cDNA clones were confirmed by expression of enzyme activity in bacteria and protein sequence data obtained from sequencing purified rat brain SSADH. PMID:7814412 Human and rat SSADH share 83 and 91% identity in nucleotide and protein sequence, respectively. PMID:16199352 The Michaelis constants K(m) for succinic semialdehyde and NAD(+) were 6.3 and 125 microM, respectively.
GO:0004777 succinate-semialdehyde dehydrogenase (NAD+) activity	IDA PMID:9683595 Two exon-skipping mutations as the molecular basis of succin...	ACCEPT	Summary: Human recombinant enzyme and patient-cell assays support SSADH activity. Reason: The full PMID:9683595 paper expresses recombinant human GST-SSADH in E. coli and measures SSADH activity in patient lymphocytes/lymphoblasts and relatives. Its splice defects and segregation link the enzyme activity to the human gene. Historical ALDH4A1 allele nomenclature in that paper refers to SSADH and does not indicate misattribution to modern ALDH4A1. Supporting Evidence: PMID:9683595 Our results provide the first evidence that 4-hydroxybutyric aciduria, resulting from SSADH deficiency, is the result of genetic defects in the human SSADH gene. PMID:16199352 The Michaelis constants K(m) for succinic semialdehyde and NAD(+) were 6.3 and 125 microM, respectively.
GO:0007417 central nervous system development	IMP PMID:9683595 Two exon-skipping mutations as the molecular basis of succin...	KEEP AS NON CORE	Summary: Retain the human disease-development association as non-core. Reason: The full PMID:9683595 study links SSADH-deficient genotypes and low enzyme activity to patients with developmental/speech delay and other neurological features. This supports the curator's phenotype-based developmental association, but the paper does not assay a particular CNS morphogenetic or differentiation step; it also reports no established correlation between residual activity or GHB level and clinical severity. Retain the existing IMP as non-core rather than adding a separate developmental core function or claiming an established developmental mechanism. The public original paper describes developmental and speech delays on journal page 407 (https://art.torvergata.it/retrieve/e291c0d3-7a76-cddb-e053-3a05fe0aa144/Chambliss_AJHG_1998.pdf); its full text remains absent from the normal local cache. Supporting Evidence: PMID:9683595 Our results provide the first evidence that 4-hydroxybutyric aciduria, resulting from SSADH deficiency, is the result of genetic defects in the human SSADH gene.
GO:0009450 GABA catabolic process	IDA PMID:9683595 Two exon-skipping mutations as the molecular basis of succin...	ACCEPT	Summary: Human SSADH activity directly contributes to GABA catabolism. Reason: PMID:9683595 links genetic defects to loss of human SSADH activity and disordered 4-aminobutyrate metabolism, including expression of active human enzyme. Together with the independently characterized SSA oxidation step (PMID:16199352), this supports direct catalytic participation in GABA degradation. Neurological phenotypes are not needed to infer this metabolic role. Supporting Evidence: PMID:9683595 Our results provide the first evidence that 4-hydroxybutyric aciduria, resulting from SSADH deficiency, is the result of genetic defects in the human SSADH gene. PMID:12208142 Mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase (ALDH5A1, SSADH) represents the last enzyme in the GABA catabolism and irreversibly oxidizes SSA to succinate.
GO:0005739 mitochondrion	ISS GO_REF:0000024	ACCEPT	Summary: Mouse-to-human mitochondrial localization transfer is supported. Reason: The donor Q8BWF0 is mouse Aldh5a1. MGI and the cached mouse GO-CAM trace its mitochondrial evidence to PMID:14651853; the individual donor proteomics row is not visible in the cached abstract. The broad transfer agrees with independent human mitochondrial matrix evidence (PMID:19300440), rather than depending solely on another electronic annotation. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8BWF0 SUPPORTS TRANSFER The mouse Aldh5a1 donor has experimental mitochondrial provenance (PMID:14651853) in MGI and GO-CAM 68d5ebd600002976. Individual peptide data were not inspected; the accepted human compartment has independent support. Supporting Evidence: PMID:19300440 Succinic semialdehyde dehydrogenase (SSADH) is involved in the final degradation step of the inhibitory neurotransmitter gamma-aminobutyric acid by converting succinic semialdehyde to succinic acid in the mitochondrial matrix.

Gene Description

Existing Annotations Review

Core Functions

As a homotetramer in the mitochondrial matrix, ALDH5A1 oxidizes succinate semialdehyde with NAD+ to produce succinate and NADH. This catalytic step completes GABA degradation and connects the glutamate/GABA shunt to central carbon metabolism.

References

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