Gcat (CG10361) encodes the Drosophila mitochondrial 2-amino-3-ketobutyrate coenzyme A ligase (glycine C-acetyltransferase, EC 2.3.1.29), a pyridoxal 5'-phosphate-dependent member of the class-II aminotransferase (alpha-oxoamine synthase) family. It catalyzes the second step of the threonine dehydrogenase pathway, cleaving 2-amino-3-oxobutanoate produced by the mitochondrial L-threonine 3-dehydrogenase (Tdh) with coenzyme A to yield glycine and acetyl-CoA, thereby linking L-threonine catabolism to glycine production in the mitochondrial matrix. Its function in flies is inferred from strong conservation with the characterized vertebrate and bacterial enzymes; no fly-specific biochemical or genetic study is available.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial localization inferred from the PANTHER ancestral node carrying the mitochondrial 2-amino-3-ketobutyrate CoA ligases. Reason: The fly protein falls in the mitochondrial GCAT subfamily (PTHR13693:SF102) and UniProt names it the mitochondrial enzyme; the threonine dehydrogenase pathway is a matrix pathway in animals, so the phylogenetic inference is sound. Supporting Evidence: file:DROME/Gcat/Gcat-uniprot.txt 2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | ACCEPT | Summary: Mitochondrial localization transferred from the bovine GCAT ortholog. Reason: Consistent with the IBA and the subfamily assignment; GCAT is a mitochondrial matrix enzyme in vertebrates. Supporting Evidence: file:DROME/Gcat/Gcat-uniprot.txt PANTHER; PTHR13693:SF102; 2-AMINO-3-KETOBUTYRATE COENZYME A LIGASE, MITOCHONDRIAL |
| GO:0006545 glycine biosynthetic process | ISS GO_REF:0000024 | ACCEPT | Summary: GCAT produces glycine from 2-amino-3-oxobutanoate and CoA, the second step of glycine formation from threonine. Reason: The fly protein matches the curated HAMAP rule and the NCBIfam TIGR01822 family for 2-amino-3-ketobutyrate CoA ligase, whose characterized members (vertebrate and bacterial) cleave 2-amino-3-oxobutanoate with CoA to glycine plus acetyl-CoA, so the enzyme directly performs a glycine-forming step. This is a family-membership argument; there is no fly-specific biochemical or genetic evidence (the record's catalytic-activity direction is an ARBA prediction and is not cited). Supporting Evidence: file:DROME/Gcat/Gcat-uniprot.txt HAMAP; MF_00985; 2am3keto_CoA_ligase; 1. file:DROME/Gcat/Gcat-uniprot.txt NCBIfam; TIGR01822; 2am3keto_CoA; 1. |
| GO:0006567 L-threonine catabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: GCAT catalyzes the second step of the TDH/GCAT threonine degradation pathway. Reason: IPR011282 (2-amino-3-ketobutyrate CoA ligase) is a specific family signature; the enzyme consumes the threonine-derived intermediate 2-amino-3-oxobutanoate. Supporting Evidence: file:DROME/Gcat/Gcat-uniprot.txt InterPro; IPR011282; 2am3keto_CoA_ligase. |
| GO:0006567 L-threonine catabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: Threonine catabolism role transferred from the bovine ortholog. Reason: Same reasoning as the InterPro-based annotation; the fly enzyme is a clear ortholog. Supporting Evidence: file:DROME/Gcat/Gcat-uniprot.txt InterPro; IPR011282; 2am3keto_CoA_ligase. |
| GO:0008890 glycine C-acetyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Core catalytic activity (EC 2.3.1.29) of the 2-amino-3-ketobutyrate CoA ligase family. Reason: Specific family signatures (InterPro IPR011282, HAMAP MF_00985, NCBIfam TIGR01822, all 2-amino-3-ketobutyrate CoA ligase) place the protein in a family whose defining activity is EC 2.3.1.29; this is the defining activity of the protein, inferred from family membership. Supporting Evidence: file:DROME/Gcat/Gcat-uniprot.txt InterPro; IPR011282; 2am3keto_CoA_ligase. file:DROME/Gcat/Gcat-uniprot.txt HAMAP; MF_00985; 2am3keto_CoA_ligase; 1. |
| GO:0008890 glycine C-acetyltransferase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Catalytic activity transferred from the bovine GCAT ortholog. Reason: Orthology to a characterized vertebrate enzyme supports the core activity; the fly protein falls in the mitochondrial GCAT PANTHER subfamily and the NCBIfam family for 2-amino-3-ketobutyrate CoA ligase (family-membership support, not fly-specific assay). Supporting Evidence: file:DROME/Gcat/Gcat-uniprot.txt PANTHER; PTHR13693:SF102; 2-AMINO-3-KETOBUTYRATE COENZYME A LIGASE, MITOCHONDRIAL file:DROME/Gcat/Gcat-uniprot.txt NCBIfam; TIGR01822; 2am3keto_CoA; 1. |
| GO:0016740 transferase activity | IEA GO_REF:0000002 | MODIFY | Summary: Generic transferase term derived from the class-II aminotransferase PLP-binding-site signature. Reason: The term is correct but uninformative; the specific activity is glycine C-acetyltransferase (an acyltransferase, not an aminotransferase). Proposed replacements: glycine C-acetyltransferase activity Supporting Evidence: file:DROME/Gcat/Gcat-uniprot.txt EC=2.3.1.29 |
| GO:0030170 pyridoxal phosphate binding | IEA GO_REF:0000002 | ACCEPT | Summary: GCAT is a PLP-dependent fold-type I enzyme that requires PLP as cofactor. Reason: PLP is the catalytic cofactor of the alpha-oxoamine synthase family; the sequence matches the PROSITE class-II aminotransferase pattern and the InterPro class-II PLP-binding-site signature, which cover the lysine that forms the Schiff base with PLP. Cofactor binding is a genuine, if subsidiary, molecular property (family/motif inference; the record's COFACTOR line is an ARBA prediction and is not cited). Supporting Evidence: file:DROME/Gcat/Gcat-uniprot.txt PROSITE; PS00599; AA_TRANSFER_CLASS_2; 1. file:DROME/Gcat/Gcat-uniprot.txt InterPro; IPR001917; Aminotrans_II_pyridoxalP_BS. |
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Download this section (compressed HTML)Q: How much of Drosophila glycine is produced through the Tdh/Gcat threonine pathway versus serine hydroxymethyltransferase, and does this vary with diet or tissue?
Q: Does Gcat physically associate with Tdh in the mitochondrial matrix to channel the unstable 2-amino-3-oxobutanoate intermediate, as proposed for the bacterial enzymes?
Experiment: Generate a Gcat null allele and measure threonine, glycine and aminoacetone by targeted metabolomics, then test sleep latency and muscle performance alongside Tdh mutants.
Hypothesis: Gcat loss in flies diverts 2-amino-3-oxobutanoate to aminoacetone and elevates threonine, phenocopying Tdh hypomorphs (for example, increased sleep drive).
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Download this section (compressed HTML)Glycine C-acetyltransferase (Gcat) encodes a mitochondrial enzyme that is predicted to catalyze the conversion of 2-amino-3-oxobutanoate and CoA to glycine and acetyl-CoA in the last step of glycine biosynthesis from L-threonine.
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