Dihydrolipoyl dehydrogenase (lipoamide dehydrogenase, E3; EC 1.8.1.4) of Saccharomyces cerevisiae, the single FAD-containing homodimeric E3 shared by all mitochondrial lipoate-dependent complexes. Lpd1 reoxidises the dihydrolipoyl arms of the pyruvate dehydrogenase (Lat1), 2-oxoglutarate dehydrogenase (Kgd2) and glycine cleavage (Gcv3, as L-protein) systems, transferring electrons to NAD+. In KGDH it is recruited to the Kgd1-Kgd2 core by Kgd4; a substantial pool is free in the matrix. lpd1 mutants lack PDH, KGDH and glycine cleavage activities, cannot grow on glycerol or acetate or on glycine as nitrogen source, and fail to sporulate. LPD1 is glucose-repressed. Lpd1-containing complexes are also a source of mitochondrial H2O2.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004148 dihydrolipoyl dehydrogenase (NADH) activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN000530299) for dihydrolipoyl dehydrogenase; Lpd1 (SGD:S000001876) is itself an experimental leaf. Supporting Evidence: PMID:2821168 The LPD1 gene of S. cerevisiae, which encodes lipoamide dehydrogenase (EC 1.8.1.4), has been cloned and characterized file:yeast/LPD1/LPD1-uniprot.txt Reaction=N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + NAD(+) = N(6)- [(R)-lipoyl]-L-lysyl-[protein] + NADH + H(+) |
| GO:0004148 dihydrolipoyl dehydrogenase (NADH) activity | IDA PMID:2821168 Cloning and characterization of the gene encoding lipoamide ... | ACCEPT | Summary: Roy & Dawes cloned LPD1 as the lipoamide dehydrogenase gene; overexpression raised lipoamide dehydrogenase activity. Supporting Evidence: PMID:2821168 The LPD1 gene of S. cerevisiae, which encodes lipoamide dehydrogenase (EC 1.8.1.4), has been cloned and characterized PMID:2821168 increased lipoamide dehydrogenase activity when grown on glycerol |
| GO:0004148 dihydrolipoyl dehydrogenase (NADH) activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (ARBA, InterPro IPR006258, RHEA:15045, EC 1.8.1.4); correct. Supporting Evidence: file:yeast/LPD1/LPD1-uniprot.txt Reaction=N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + NAD(+) = N(6)- [(R)-lipoyl]-L-lysyl-[protein] + NADH + H(+) |
| GO:0004148 dihydrolipoyl dehydrogenase (NADH) activity | IMP PMID:3528755 A mutation affecting lipoamide dehydrogenase, pyruvate dehyd... | ACCEPT | Summary: lpd1 mutation abolishes lipoamide dehydrogenase activity and the activities of the E3-dependent complexes. Supporting Evidence: PMID:3528755 a nuclear recessive mutation, lpd1, which simultaneously abolishes the activities of lipoamide dehydrogenase, 2-oxoglutarate dehydrogenase and pyruvate dehydrogenase has been identified |
| GO:0004148 dihydrolipoyl dehydrogenase (NADH) activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from glycine cleavage (GLYCLEAV-PWY); Lpd1 is the L-protein that reoxidises the H-protein dihydrolipoyl arm. Correct reaction assignment. Supporting Evidence: PMID:7498764 Yeast strains with mutations in the single gene for lipoamide dehydrogenase (lpd1) lack GDC activity, as well as the other three 2-oxoacid dehydrogenases dependent on this enzyme file:yeast/LPD1/LPD1-uniprot.txt Also acts as a component of the glycine cleavage system (glycine decarboxylase complex), which catalyzes the degradation of glycine (PubMed:7498764). |
| GO:0004148 dihydrolipoyl dehydrogenase (NADH) activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from 2-oxoglutarate decarboxylation to succinyl-CoA (PWY-5084); E3 of KGDH. Correct. Supporting Evidence: PMID:3528755 a nuclear recessive mutation, lpd1, which simultaneously abolishes the activities of lipoamide dehydrogenase, 2-oxoglutarate dehydrogenase and pyruvate dehydrogenase has been identified PMID:25165143 Kgd4 is specifically necessary for stably recruiting the E3 subunit Lpd1 to the Kgd1-Kgd2 subcomplex |
| GO:0004148 dihydrolipoyl dehydrogenase (NADH) activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from pyruvate dehydrogenase (PYRUVDEHYD-PWY); E3 of PDH. Correct. Supporting Evidence: PMID:3528755 a nuclear recessive mutation, lpd1, which simultaneously abolishes the activities of lipoamide dehydrogenase, 2-oxoglutarate dehydrogenase and pyruvate dehydrogenase has been identified PMID:12756305 cerevisiae PDC is ≈24 E 1 tetramers, 60 E 2 monomers, 12 BP monomers, and 8 E 3 dimers |
| GO:0004375 glycine dehydrogenase (decarboxylating) activity | IMP PMID:7498764 Genetics of the synthesis of serine from glycine and the uti... | MODIFY | Summary: Sinclair & Dawes show lpd1 mutants lack overall GDC activity. Lpd1 is the L-protein, however; the glycine dehydrogenase (decarboxylating) reaction (EC 1.4.4.2) is catalysed by the P-protein Gcv2. Loss of the whole-complex activity reflects Lpd1's own dihydrolipoyl dehydrogenase step within GCS, not glycine decarboxylation by Lpd1. Reason: The activity belongs to Gcv2; Lpd1 enables the E3 step of the complex. At most this could be contributes_to. Proposed replacements: dihydrolipoyl dehydrogenase (NADH) activity Supporting Evidence: PMID:7498764 Yeast strains with mutations in the single gene for lipoamide dehydrogenase (lpd1) lack GDC activity, as well as the other three 2-oxoacid dehydrogenases dependent on this enzyme PMID:7498764 The effect of mutations in LPD1 (L-subunit of GDC) |
| GO:0004591 oxoglutarate dehydrogenase (succinyl-transferring) activity | IMP PMID:3528755 A mutation affecting lipoamide dehydrogenase, pyruvate dehyd... | MODIFY | Summary: Dickinson et al. show that lpd1 abolishes 2-oxoglutarate dehydrogenase activity. GO:0004591 is the E1 (Kgd1) activity; Lpd1 performs the E3 reoxidation of the dihydrolipoyl-Kgd2 arm. The phenotype shows that Lpd1 is required for the complex, not that it catalyses the E1 reaction. Reason: E1 activity belongs to Kgd1; Lpd1's own activity is E3. Proposed replacements: dihydrolipoyl dehydrogenase (NADH) activity Supporting Evidence: PMID:3528755 a nuclear recessive mutation, lpd1, which simultaneously abolishes the activities of lipoamide dehydrogenase, 2-oxoglutarate dehydrogenase and pyruvate dehydrogenase has been identified |
| GO:0004591 oxoglutarate dehydrogenase (succinyl-transferring) activity | RCA GO_REF:0000123 | MODIFY | Summary: YeastPathways RCA with contributes_to qualifier for the KGDH overall reaction (TCA-EUK-PWY). The contributes_to qualifier records that Lpd1 is a subunit of the 2-oxoglutarate dehydrogenase complex, but GO:0004591 is the E1 reaction (oxidative decarboxylation of 2-oxoglutarate onto the lipoyl arm of the E2), which Kgd1 catalyses. Reason: Treated the same way as the IMP row for this term. The E3 subunit does not contribute to the E1 reaction itself; it reoxidizes the dihydrolipoyl arm left by the E2 succinyltransferase. Lpd1's own contribution is the E3 activity GO:0004148, already accepted on this gene. Proposed replacements: dihydrolipoyl dehydrogenase (NADH) activity Supporting Evidence: PMID:3528755 a nuclear recessive mutation, lpd1, which simultaneously abolishes the activities of lipoamide dehydrogenase, 2-oxoglutarate dehydrogenase and pyruvate dehydrogenase has been identified PMID:25165143 In lysates from wild-type mitochondria, Kgd1, Kgd2, Lpd1, and Kgd4 comigrated |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | REMOVE | Summary: High-throughput affinity-purification/MS or interactome data recovering Lpd1 with Kgd2 (P19262, E2 dihydrolipoyllysine succinyltransferase). The interaction is physiological (E3 is docked on the E2 core of KGDH), but 'protein binding' adds nothing beyond the complex-membership annotations (GO:0045252 oxoglutarate dehydrogenase complex), which already capture it. Reason: Uninformative generic protein binding; the interaction is real and is captured by part_of oxoglutarate dehydrogenase complex. Supporting Evidence: PMID:16429126 using affinity purification and mass spectrometry PMID:2072900 mutants lacking KE1 assemble a high-molecular-weight subcomplex consisting of a KE2 core particle with bound dihydrolipoyl dehydrogenase (E3) |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | REMOVE | Summary: High-throughput affinity-purification/MS or interactome data recovering Lpd1 with Kgd4 (P19955, Ymr31/MRPS36). The interaction is physiological (Kgd4 is the adaptor that recruits E3 to the KGDH E1-E2 core), but 'protein binding' adds nothing beyond the complex-membership annotations (GO:0045252 oxoglutarate dehydrogenase complex), which already capture it. Reason: Uninformative generic protein binding; the interaction is real and is captured by part_of oxoglutarate dehydrogenase complex. Supporting Evidence: PMID:16429126 using affinity purification and mass spectrometry PMID:25165143 showed that Kgd4 directly binds to Lpd1 |
| GO:0005515 protein binding | IPI PMID:25165143 The novel component Kgd4 recruits the E3 subunit to the mito... | REMOVE | Summary: Heublein et al. show Lpd1 crosslinks to Kgd2 inside KGDH. Real interaction, but generic protein binding. Reason: Uninformative generic protein binding; the interaction is real and is captured by part_of oxoglutarate dehydrogenase complex. Supporting Evidence: PMID:25165143 In lysates from wild-type mitochondria, Kgd1, Kgd2, Lpd1, and Kgd4 comigrated |
| GO:0005515 protein binding | IPI PMID:25165143 The novel component Kgd4 recruits the E3 subunit to the mito... | REMOVE | Summary: Heublein et al. show Kgd4 directly binds Lpd1 and recruits it to KGDH. Real, but better expressed as complex membership; 'protein binding' is uninformative. Reason: Uninformative generic protein binding; the interaction is real and is captured by part_of oxoglutarate dehydrogenase complex. Supporting Evidence: PMID:25165143 showed that Kgd4 directly binds to Lpd1 PMID:25165143 Kgd4 is specifically necessary for stably recruiting the E3 subunit Lpd1 to the Kgd1-Kgd2 subcomplex |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: High-throughput affinity-purification/MS or interactome data recovering Lpd1 with Kgd2 (P19262, E2 dihydrolipoyllysine succinyltransferase). The interaction is physiological (E3 is docked on the E2 core of KGDH), but 'protein binding' adds nothing beyond the complex-membership annotations (GO:0045252 oxoglutarate dehydrogenase complex), which already capture it. Reason: Uninformative generic protein binding; the interaction is real and is captured by part_of oxoglutarate dehydrogenase complex. Supporting Evidence: PMID:25165143 In lysates from wild-type mitochondria, Kgd1, Kgd2, Lpd1, and Kgd4 comigrated |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: High-throughput affinity-purification/MS or interactome data recovering Lpd1 with Kgd4 (P19955, Ymr31/MRPS36). The interaction is physiological (Kgd4 is the adaptor that recruits E3 to the KGDH E1-E2 core), but 'protein binding' adds nothing beyond the complex-membership annotations (GO:0045252 oxoglutarate dehydrogenase complex), which already capture it. Reason: Uninformative generic protein binding; the interaction is real and is captured by part_of oxoglutarate dehydrogenase complex. Supporting Evidence: PMID:25165143 showed that Kgd4 directly binds to Lpd1 |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Lpd1 in the PROMITO mitochondrial proteome (is_active_in row). Supporting Evidence: PMID:16823961 A total of 851 different proteins (PROMITO dataset) were identified by use of multidimensional LC-MS/MS, 1D-SDS-PAGE combined with nano-LC-MS/MS and 2D-PAGE with subsequent MALDI-mass fingerprinting. |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Lpd1 in the PROMITO mitochondrial proteome. Supporting Evidence: PMID:16823961 A total of 851 different proteins (PROMITO dataset) were identified by use of multidimensional LC-MS/MS, 1D-SDS-PAGE combined with nano-LC-MS/MS and 2D-PAGE with subsequent MALDI-mass fingerprinting. |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: Lpd1 quantified in the mitochondrial proteome across growth conditions. Supporting Evidence: PMID:24769239 The yeast Saccharomyces cerevisiae is a facultative aerobe able to adapt its metabolism according to the carbon substrate |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for mitochondrial DLD; consistent with experimental localisation. Supporting Evidence: PMID:25165143 a substantial amount of Lpd1 exists in a free form in the matrix |
| GO:0005739 mitochondrion | IDA PMID:18180296 Yeast pyruvate dehydrogenase complex is regulated by a conce... | ACCEPT | Summary: Gey et al. analysed PDH complex components in isolated mitochondria; curator IDA accepted. Supporting Evidence: PMID:18180296 The activity of yeast pyruvate dehydrogenase complex is regulated by reversible phosphorylation |
| GO:0005739 mitochondrion | IDA PMID:25165143 The novel component Kgd4 recruits the E3 subunit to the mito... | ACCEPT | Summary: Heublein et al. purified Lpd1 from isolated mitochondria and found it both in KGDH and free in the matrix. Supporting Evidence: PMID:25165143 In lysates from wild-type mitochondria, Kgd1, Kgd2, Lpd1, and Kgd4 comigrated PMID:25165143 a substantial amount of Lpd1 exists in a free form in the matrix |
| GO:0005739 mitochondrion | NAS PMID:8830251 Specific induction by glycine of the gene for the P-subunit ... | ACCEPT | Summary: Author statement on mitochondrial GDC (includes L-protein); correct. Supporting Evidence: PMID:8830251 The levels of P- and L-protein transcripts and GDC activity were also elevated in cells grown in the presence of glycine |
| GO:0005739 mitochondrion | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY-5084, 2-oxoglutarate decarboxylation); mitochondrial, correct. Supporting Evidence: PMID:25165143 In lysates from wild-type mitochondria, Kgd1, Kgd2, Lpd1, and Kgd4 comigrated |
| GO:0005739 mitochondrion | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (TCA-EUK-PWY); mitochondrial, correct. Supporting Evidence: PMID:25165143 In lysates from wild-type mitochondria, Kgd1, Kgd2, Lpd1, and Kgd4 comigrated |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell mapping to mitochondrial matrix; matches free and complex-bound matrix pools. Supporting Evidence: file:yeast/LPD1/LPD1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix. PMID:25165143 a substantial amount of Lpd1 exists in a free form in the matrix |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA (GLYCLEAV-PWY) placing activity in the cytosol, the conversion's default compartment. Yeast glycine cleavage is mitochondrial and Lpd1 is a matrix protein. Reason: Default-compartment artefact; no cytosolic Lpd1 activity is known. Supporting Evidence: file:yeast/LPD1/LPD1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA (PYRUVDEHYD-PWY) placing PDH activity in the cytosol. Yeast PDH is a mitochondrial matrix complex. Reason: Default-compartment artefact; PDH and Lpd1 are mitochondrial. Supporting Evidence: file:yeast/LPD1/LPD1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix. |
| GO:0005960 glycine cleavage complex | IMP PMID:7498764 Genetics of the synthesis of serine from glycine and the uti... | ACCEPT | Summary: lpd1 mutants lack GDC activity and cannot use glycine as N source; Lpd1 is the GDC L-protein. Supporting Evidence: PMID:7498764 Yeast strains with mutations in the single gene for lipoamide dehydrogenase (lpd1) lack GDC activity, as well as the other three 2-oxoacid dehydrogenases dependent on this enzyme PMID:7498764 The effect of mutations in LPD1 (L-subunit of GDC) |
| GO:0005960 glycine cleavage complex | NAS PMID:7498764 Genetics of the synthesis of serine from glycine and the uti... | ACCEPT | Summary: NAS from the same paper; Lpd1 is the L-subunit of GDC. Supporting Evidence: PMID:7498764 The effect of mutations in LPD1 (L-subunit of GDC) |
| GO:0006086 pyruvate decarboxylation to acetyl-CoA | NAS PMID:18180296 Yeast pyruvate dehydrogenase complex is regulated by a conce... | ACCEPT | Summary: NAS (Gey et al., PDH regulation); Lpd1 is E3 of PDH, which converts pyruvate to acetyl-CoA. Supporting Evidence: PMID:3528755 a nuclear recessive mutation, lpd1, which simultaneously abolishes the activities of lipoamide dehydrogenase, 2-oxoglutarate dehydrogenase and pyruvate dehydrogenase has been identified PMID:18180296 The activity of yeast pyruvate dehydrogenase complex is regulated by reversible phosphorylation |
| GO:0006086 pyruvate decarboxylation to acetyl-CoA | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PYRUVDEHYD-PWY); correct. Supporting Evidence: PMID:3528755 a nuclear recessive mutation, lpd1, which simultaneously abolishes the activities of lipoamide dehydrogenase, 2-oxoglutarate dehydrogenase and pyruvate dehydrogenase has been identified |
| GO:0006099 tricarboxylic acid cycle | NAS PMID:25165143 The novel component Kgd4 recruits the E3 subunit to the mito... | MODIFY | Summary: NAS: Lpd1 is E3 of KGDH, a TCA-cycle enzyme complex. Reason: Correct but general: the E3 takes part in the tricarboxylic acid cycle only through the 2-oxoglutarate dehydrogenase step, reoxidizing the E2 lipoyl arm during oxidative decarboxylation of 2-oxoglutarate to succinyl-CoA. GO:0120551 is part_of the TCA cycle and is the supported refinement, as in the DLD review. Proposed replacements: 2-oxoglutarate decarboxylation to succinyl-CoA Supporting Evidence: PMID:25165143 In lysates from wild-type mitochondria, Kgd1, Kgd2, Lpd1, and Kgd4 comigrated |
| GO:0006103 2-oxoglutarate metabolic process | IBA GO_REF:0000033 | MODIFY | Summary: True but broad; the E3 acts in OGDH-catalysed 2-oxoglutarate decarboxylation. Reason: Correct but general: the E3 takes part in 2-oxoglutarate metabolism by reoxidizing the lipoyl arm of the 2-oxoglutarate dehydrogenase E2 during oxidative decarboxylation of 2-oxoglutarate to succinyl-CoA. MODIFY to GO:0120551, as in the DLD and E. coli lpd reviews. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000530299 · PANTHER:PTN000530299 SUPPORTS TRANSFER The PAINT node supports the conserved OGDH E3 role; the row is narrowed from the broad parent process to the exact OGDH step. Proposed replacements: 2-oxoglutarate decarboxylation to succinyl-CoA Supporting Evidence: PMID:25165143 In lysates from wild-type mitochondria, Kgd1, Kgd2, Lpd1, and Kgd4 comigrated |
| GO:0006103 2-oxoglutarate metabolic process | IDA PMID:25165143 The novel component Kgd4 recruits the E3 subunit to the mito... | MODIFY | Summary: True but broad; the E3 acts in OGDH-catalysed 2-oxoglutarate decarboxylation. Reason: Correct but general: the E3 takes part in 2-oxoglutarate metabolism by reoxidizing the lipoyl arm of the 2-oxoglutarate dehydrogenase E2 during oxidative decarboxylation of 2-oxoglutarate to succinyl-CoA. MODIFY to GO:0120551, as in the DLD and E. coli lpd reviews. Proposed replacements: 2-oxoglutarate decarboxylation to succinyl-CoA Supporting Evidence: PMID:25165143 In lysates from wild-type mitochondria, Kgd1, Kgd2, Lpd1, and Kgd4 comigrated |
| GO:0006103 2-oxoglutarate metabolic process | IMP PMID:3528755 A mutation affecting lipoamide dehydrogenase, pyruvate dehyd... | MODIFY | Summary: True but broad; the E3 acts in OGDH-catalysed 2-oxoglutarate decarboxylation. Reason: Correct but general: the E3 takes part in 2-oxoglutarate metabolism by reoxidizing the lipoyl arm of the 2-oxoglutarate dehydrogenase E2 during oxidative decarboxylation of 2-oxoglutarate to succinyl-CoA. MODIFY to GO:0120551, as in the DLD and E. coli lpd reviews. Proposed replacements: 2-oxoglutarate decarboxylation to succinyl-CoA Supporting Evidence: PMID:25165143 In lysates from wild-type mitochondria, Kgd1, Kgd2, Lpd1, and Kgd4 comigrated |
| GO:0006546 glycine catabolic process | IMP PMID:7498764 Genetics of the synthesis of serine from glycine and the uti... | MODIFY | Summary: True but broad parent of the glycine cleavage process. Reason: Correct but general: glycine catabolic process is an ancestor of GO:0019464 glycine decarboxylation via glycine cleavage system, which this gene already carries and which is the process the gene product directly performs a step of. MODIFY to that descendant; applied the same way to every P-, H-, T- and L-protein review in the glycine cleavage system module. Proposed replacements: glycine decarboxylation via glycine cleavage system Supporting Evidence: PMID:7498764 Yeast strains with mutations in the single gene for lipoamide dehydrogenase (lpd1) lack GDC activity, as well as the other three 2-oxoacid dehydrogenases dependent on this enzyme |
| GO:0006546 glycine catabolic process | NAS PMID:7498764 Genetics of the synthesis of serine from glycine and the uti... | MODIFY | Summary: True but broad parent of the glycine cleavage process. Reason: Correct but general: glycine catabolic process is an ancestor of GO:0019464 glycine decarboxylation via glycine cleavage system, which this gene already carries and which is the process the gene product directly performs a step of. MODIFY to that descendant; applied the same way to every P-, H-, T- and L-protein review in the glycine cleavage system module. Proposed replacements: glycine decarboxylation via glycine cleavage system Supporting Evidence: PMID:7498764 Yeast strains with mutations in the single gene for lipoamide dehydrogenase (lpd1) lack GDC activity, as well as the other three 2-oxoacid dehydrogenases dependent on this enzyme |
| GO:0006550 L-isoleucine catabolic process | IMP PMID:1479341 The catabolism of branched-chain amino acids occurs via 2-ox... | KEEP AS NON CORE | Summary: Dickinson & Dawes reported a lipoamide-dehydrogenase-dependent branched-chain 2-oxoacid dehydrogenase activity in yeast and loss of BCAA catabolism in lpd1 mutants. S. cerevisiae lacks clear orthologues of the mammalian BCKDH E1/E2 subunits and fusel-alcohol (Ehrlich) catabolism dominates, so the physiological weight of this route is uncertain; kept as non-core rather than overruling the curator. Supporting Evidence: PMID:1479341 Mutants defective in lipoamide dehydrogenase also lack 2-oxoacid dehydrogenase and are thus unable to catabolize branched-chain amino acids |
| GO:0006552 L-leucine catabolic process | IMP PMID:1479341 The catabolism of branched-chain amino acids occurs via 2-ox... | KEEP AS NON CORE | Summary: As for isoleucine: lpd1 mutants accumulate branched-chain 2-oxoacids. Non-core, mechanism (which E1/E2 partner) unresolved. Supporting Evidence: PMID:1479341 Mutants defective in lipoamide dehydrogenase also lack 2-oxoacid dehydrogenase and are thus unable to catabolize branched-chain amino acids |
| GO:0006564 L-serine biosynthetic process | IMP PMID:7498764 Genetics of the synthesis of serine from glycine and the uti... | KEEP AS NON CORE | Summary: Serine synthesis from glycine requires GDC-derived 5,10-CH2-THF, and lpd1 blocks it. Lpd1 contributes indirectly (reoxidising the H-protein); serine is formed by Shm1/Shm2. Non-core. Supporting Evidence: PMID:7498764 can convert glycine to serine via the reaction catalyzed by the glycine decarboxylase multienzyme complex (GDC) PMID:7498764 Yeast strains with mutations in the single gene for lipoamide dehydrogenase (lpd1) lack GDC activity, as well as the other three 2-oxoacid dehydrogenases dependent on this enzyme |
| GO:0006574 L-valine catabolic process | IMP PMID:1479341 The catabolism of branched-chain amino acids occurs via 2-ox... | KEEP AS NON CORE | Summary: As for other BCAAs; lpd1 blocks valine-derived 2-oxoacid oxidation. Non-core. Supporting Evidence: PMID:1479341 Mutants defective in lipoamide dehydrogenase also lack 2-oxoacid dehydrogenase and are thus unable to catabolize branched-chain amino acids |
| GO:0009060 aerobic respiration | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways RCA (TCA-EUK-PWY) to aerobic respiration; true via KGDH in the TCA cycle but broad. Supporting Evidence: PMID:3528755 are unable to grow on media with glycerol or acetate as carbon source |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | MODIFY | Summary: True but broad parent of the specific E3 activity. Reason: Correct but general: oxidoreductase activity is an ancestor of GO:0004148 dihydrolipoyl dehydrogenase (NADH) activity, which this gene carries with direct support. MODIFY to that descendant, as in the other L-protein reviews of the module. Proposed replacements: dihydrolipoyl dehydrogenase (NADH) activity Supporting Evidence: PMID:2821168 The LPD1 gene of S. cerevisiae, which encodes lipoamide dehydrogenase (EC 1.8.1.4), has been cloned and characterized |
| GO:0016668 oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor | IEA GO_REF:0000002 | MODIFY | Summary: True but broad parent of the specific E3 activity. Reason: Correct but general: oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor is an ancestor of GO:0004148 dihydrolipoyl dehydrogenase (NADH) activity, which this gene carries with direct support. MODIFY to that descendant, as in the other L-protein reviews of the module. Proposed replacements: dihydrolipoyl dehydrogenase (NADH) activity Supporting Evidence: PMID:2821168 The LPD1 gene of S. cerevisiae, which encodes lipoamide dehydrogenase (EC 1.8.1.4), has been cloned and characterized |
| GO:0019464 glycine decarboxylation via glycine cleavage system | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (GLYCLEAV-PWY); Lpd1 is the GDC L-protein. Supporting Evidence: PMID:7498764 Yeast strains with mutations in the single gene for lipoamide dehydrogenase (lpd1) lack GDC activity, as well as the other three 2-oxoacid dehydrogenases dependent on this enzyme |
| GO:0042645 mitochondrial nucleoid | IDA PMID:10869431 In organello formaldehyde crosslinking of proteins to mtDNA:... | KEEP AS NON CORE | Summary: Kaufman et al. formaldehyde crosslinking of proteins to mtDNA; the abstract highlights Kgd2, and the curator recorded Lpd1 from the full text. Consistent with KGDH association with nucleoids. Non-core. Supporting Evidence: PMID:10869431 we have developed an in organello formaldehyde crosslinking procedure to identify proteins associated with mtDNA |
| GO:0042645 mitochondrial nucleoid | IDA PMID:11926067 Identification of the YMN-1 antigen protein and biochemical ... | KEEP AS NON CORE | Summary: Sato et al. detected E3 with KGDH in the mt-nucleoid fraction. Non-core localisation. Supporting Evidence: PMID:11926067 alpha-Ketoglutarate dehydrogenase (KE1) and dihydrolipoyl dehydrogenase (E3), which are other subunits of KGDC, were also detected in the mt-nucleoid fraction |
| GO:0042743 hydrogen peroxide metabolic process | IGI PMID:17110466 Dihydrolipoyl dehydrogenase as a source of reactive oxygen s... | KEEP AS NON CORE | Summary: Tahara et al.: Lpd1-containing complexes are a source of mitochondrial H2O2; lpd1 deletion suppresses oxidative stress of NAD+-salvage mutants (IGI with NPT1). This is a side-reaction of the flavoenzyme, not a physiological H2O2 metabolic role. Supporting Evidence: PMID:17110466 matrix-soluble dihydrolipoyl-dehydrogenases are an important source of CR-preventable mitochondrial reactive oxygen species (ROS) PMID:17110466 deletion of the LPD1 gene prevented oxidative stress in npt1delta and bna6delta mutants |
| GO:0042743 hydrogen peroxide metabolic process | IGI PMID:17110466 Dihydrolipoyl dehydrogenase as a source of reactive oxygen s... | KEEP AS NON CORE | Summary: Same study, IGI with BNA6. ROS production as side activity; non-core. Supporting Evidence: PMID:17110466 deletion of the LPD1 gene prevented oxidative stress in npt1delta and bna6delta mutants |
| GO:0042743 hydrogen peroxide metabolic process | IMP PMID:17110466 Dihydrolipoyl dehydrogenase as a source of reactive oxygen s... | KEEP AS NON CORE | Summary: Same study, IMP. Non-core. Supporting Evidence: PMID:17110466 matrix-soluble dihydrolipoyl-dehydrogenases are an important source of CR-preventable mitochondrial reactive oxygen species (ROS) |
| GO:0045252 oxoglutarate dehydrogenase complex | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for KGDH complex membership; correct. Supporting Evidence: PMID:25165143 In lysates from wild-type mitochondria, Kgd1, Kgd2, Lpd1, and Kgd4 comigrated |
| GO:0045252 oxoglutarate dehydrogenase complex | IDA PMID:2072900 In vivo assembly of yeast mitochondrial alpha-ketoglutarate ... | ACCEPT | Summary: Repetto & Tzagoloff: E3 is bound to the KE2 core in assembled KGDC. Supporting Evidence: PMID:2072900 mutants lacking KE1 assemble a high-molecular-weight subcomplex consisting of a KE2 core particle with bound dihydrolipoyl dehydrogenase (E3) |
| GO:0045252 oxoglutarate dehydrogenase complex | IPI PMID:25165143 The novel component Kgd4 recruits the E3 subunit to the mito... | ACCEPT | Summary: Heublein et al.: Lpd1 comigrates with Kgd1, Kgd2 and Kgd4 and is recruited by Kgd4. Supporting Evidence: PMID:25165143 In lysates from wild-type mitochondria, Kgd1, Kgd2, Lpd1, and Kgd4 comigrated PMID:25165143 Kgd4 is specifically necessary for stably recruiting the E3 subunit Lpd1 to the Kgd1-Kgd2 subcomplex |
| GO:0045254 pyruvate dehydrogenase complex | IDA PMID:12756305 3D electron microscopy reveals the variable deposition and p... | ACCEPT | Summary: Gu et al. cryo-EM of yeast PDC including the E3 component (8 E3 dimers per complex). Supporting Evidence: PMID:12756305 cerevisiae PDC is ≈24 E 1 tetramers, 60 E 2 monomers, 12 BP monomers, and 8 E 3 dimers |
| GO:0045254 pyruvate dehydrogenase complex | IPI PMID:18180296 Yeast pyruvate dehydrogenase complex is regulated by a conce... | ACCEPT | Summary: Gey et al.: Lpd1 co-purifies with the PDH complex; curator IPI accepted. Supporting Evidence: PMID:18180296 The activity of yeast pyruvate dehydrogenase complex is regulated by reversible phosphorylation |
| GO:0045333 cellular respiration | IMP PMID:3528755 A mutation affecting lipoamide dehydrogenase, pyruvate dehyd... | KEEP AS NON CORE | Summary: lpd1 mutants cannot grow on glycerol or acetate; respiratory growth requires PDH/KGDH. Broad process; non-core. Supporting Evidence: PMID:3528755 are unable to grow on media with glycerol or acetate as carbon source |
| GO:0045333 cellular respiration | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways RCA (PWY-5084) to cellular respiration; broad. Non-core. Supporting Evidence: PMID:3528755 are unable to grow on media with glycerol or acetate as carbon source |
| GO:0050660 flavin adenine dinucleotide binding | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for FAD binding; DLD is an FAD flavoprotein (1 FAD per subunit). Supporting Evidence: file:yeast/LPD1/LPD1-uniprot.txt Note=Binds 1 FAD per subunit. |
| GO:0050660 flavin adenine dinucleotide binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO FAD binding; correct. Supporting Evidence: file:yeast/LPD1/LPD1-uniprot.txt Note=Binds 1 FAD per subunit. |
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Download this section (compressed HTML)Q: Which E1/E2 proteins, if any, form the Lpd1-dependent branched-chain 2-oxoacid dehydrogenase activity reported in S. cerevisiae, given the absence of clear BCKDH E1/E2 orthologues?
Experiment: Measure branched-chain 2-oxoacid dehydrogenase activity in kgd1, kgd2, pda1 and lat1 single and double deletions to identify which E1/E2 components pair with Lpd1.
Dihydrolipoamide dehydrogenase; the lipoamide dehydrogenase component (E3) of the pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase multi-enzyme complexes; PDH complex is concentrated in spots within the mitochondrial matrix, often near the ERMES complex and near peroxisomes; LPD1 has a paralog, IRC15, that arose from the whole genome duplication
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