Tdh (CG5955) encodes the Drosophila mitochondrial L-threonine 3-dehydrogenase (EC 1.1.1.103), an NAD(+)-dependent short-chain dehydrogenase of the NAD(P)-dependent epimerase/dehydratase family. It catalyzes the first step of the threonine dehydrogenase pathway, oxidizing L-threonine to 2-amino-3-oxobutanoate, which the downstream ligase Gcat converts to glycine and acetyl-CoA. Hypomorphic Tdh mutants accumulate threonine and show increased sleep drive, and Tdh is among the glycine-metabolism genes induced by time-restricted feeding whose muscle-specific knockdown impairs flight muscle function and causes ectopic lipid accumulation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | ACCEPT | Summary: Mitochondrial localization transferred from the pig TDH ortholog. Reason: The fly protein belongs to the mitochondrial TDH subfamily (PTHR42687:SF1) and the threonine dehydrogenase pathway operates in the mitochondrial matrix in animals. Supporting Evidence: file:DROME/Tdh/Tdh-uniprot.txt L-threonine 3-dehydrogenase, mitochondrial |
| GO:0006545 glycine biosynthetic process | TAS PMID:36810287 Time-restricted feeding promotes muscle function through pur... | ACCEPT | Summary: Tdh performs the first of the two enzymatic steps that convert L-threonine into glycine. Reason: Tdh produces 2-amino-3-oxobutanoate, which Gcat cleaves to glycine; the cited paper groups Tdh (CG5955) with the glycine-producing genes. Tdh catalyzes a committed step of glycine formation from threonine, so it does part of the work of the process. Supporting Evidence: PMID:36810287 genes related to glycine production (Sardh and CG5955) |
| GO:0006567 L-threonine catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Threonine catabolism inherited from the PANTHER TDH ancestral node; the fly gene's own IMP evidence is one of the descendant sources. Reason: Consistent with the fly IMP data (a hypomorphic CG5955 allele raises threonine levels, PMID:31313987) and with membership of the mitochondrial L-threonine 3-dehydrogenase subfamily (PANTHER PTHR42687:SF1) that the PAINT node covers. The UniProt FUNCTION line is an ARBA prediction and is not cited. Supporting Evidence: PMID:31313987 CG5955 mutants trans-heterozygous for the hypomorphic allele over chromosomal deficiency displayed a higher ratio of threonine to total protein levels than heterozygous controls file:DROME/Tdh/Tdh-uniprot.txt DR PANTHER; PTHR42687:SF1; L-THREONINE 3-DEHYDROGENASE, MITOCHONDRIAL; 1. |
| GO:0006567 L-threonine catabolic process | IMP PMID:31313987 Sleep-promoting effects of threonine link amino acid metabol... | ACCEPT | Summary: A hypomorphic CG5955 allele lowers transcript levels and raises endogenous threonine. Reason: Direct fly genetic evidence that Tdh is required to degrade threonine, consistent with its catalytic activity. Supporting Evidence: PMID:31313987 CG5955 mutants trans-heterozygous for the hypomorphic allele over chromosomal deficiency displayed a higher ratio of threonine to total protein levels than heterozygous controls |
| GO:0006567 L-threonine catabolic process | TAS PMID:36810287 Time-restricted feeding promotes muscle function through pur... | ACCEPT | Summary: Traceable author statement placing Tdh in threonine-to-glycine metabolism. Reason: Correct process for this enzyme, redundant with the IMP and IBA rows. Supporting Evidence: PMID:36810287 shared a role in glycine utilization and production |
| GO:0008743 L-threonine 3-dehydrogenase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core catalytic activity inherited from the TDH ancestral node. Reason: The fly protein is in the L-threonine 3-dehydrogenase subfamily (PANTHER PTHR42687:SF1) inherited from the PAINT node, and carries the NAD-dependent epimerase/dehydratase Pfam domain (PF01370). The activity has not been assayed for the fly enzyme; the cited paper states it from homology, and its threonine-accumulation phenotype is consistent with it. The UniProt FUNCTION line is an ARBA prediction and is not cited. Supporting Evidence: file:DROME/Tdh/Tdh-uniprot.txt DR PANTHER; PTHR42687:SF1; L-THREONINE 3-DEHYDROGENASE, MITOCHONDRIAL; 1. file:DROME/Tdh/Tdh-uniprot.txt DR Pfam; PF01370; Epimerase; 1. PMID:31313987 CG5955 is a fly homolog of threonine 3-dehydrogenase that converts threonine and NAD+ into L-2-amino-acetoacetate, NADH, and H+ |
| GO:0008743 L-threonine 3-dehydrogenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC 1.1.1.103 mapping to the core activity. Reason: Consistent with family membership (PANTHER PTHR42687:SF1, L-threonine 3-dehydrogenase, mitochondrial) and the threonine-accumulation phenotype of mutants; the activity is stated from homology in PMID:31313987, not measured. The EC number in the UniProt name line is an ARBA label and is not cited. Supporting Evidence: file:DROME/Tdh/Tdh-uniprot.txt DR PANTHER; PTHR42687:SF1; L-THREONINE 3-DEHYDROGENASE, MITOCHONDRIAL; 1. PMID:31313987 CG5955 is a fly homolog of threonine 3-dehydrogenase that converts threonine and NAD+ into L-2-amino-acetoacetate, NADH, and H+ |
| GO:0008743 L-threonine 3-dehydrogenase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Activity transferred from the characterized mouse TDH ortholog. Reason: Clear orthology to the characterized mammalian enzyme. Supporting Evidence: PMID:31313987 CG5955 is a fly homolog of threonine 3-dehydrogenase that converts threonine and NAD+ into L-2-amino-acetoacetate, NADH, and H+ |
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Download this section (compressed HTML)Q: Is Tdh catalytic activity required in neurons specifically for the sleep phenotype, or does elevated circulating threonine from peripheral tissues drive it?
Q: Does Tdh contribute substantially to glycine pools in flight muscle, where its knockdown impairs function, or is the muscle phenotype due to threonine accumulation?
Experiment: Rescue Tdh mutants with wild-type versus catalytically inactive (NAD-binding motif mutant) Tdh transgenes and measure threonine, glycine, sleep latency and flight performance.
Hypothesis: The muscle and sleep phenotypes of Tdh loss depend on its dehydrogenase activity.
L-threonine dehydrogenase (Tdh) encodes a mitochondrial enzyme that catalyzes the oxidation of L-threonine to 2-amino-3-oxobutanoate in the first step of glycine biosynthesis from L-threonine.
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