MGP Database

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MGP002228

UniProt Annotations

Entry Information
Gene Namepyruvate dehydrogenase (lipoamide) alpha 1
Protein EntryODPA_HUMAN
UniProt IDP08559
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=4; Name=1; IsoId=P08559-1; Sequence=Displayed; Name=2; IsoId=P08559-2; Sequence=VSP_042569; Note=No experimental confirmation available.; Name=3; IsoId=P08559-3; Sequence=VSP_042570; Note=No experimental confirmation available.; Name=4; IsoId=P08559-4; Sequence=VSP_043363;
Catalytic ActivityPyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO(2). {ECO:0000269|PubMed:17474719, ECO:0000269|PubMed:19081061, ECO:0000269|PubMed:7782287}.
CofactorName=thiamine diphosphate; Xref=ChEBI:CHEBI:58937; Evidence={ECO:0000269|PubMed:12651851, ECO:0000269|PubMed:19081061};
DiseasePyruvate dehydrogenase E1-alpha deficiency (PDHAD) [MIM:312170]: An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis. {ECO:0000269|PubMed:1293379, ECO:0000269|PubMed:1338114, ECO:0000269|PubMed:1551669, ECO:0000269|PubMed:1909401, ECO:0000269|PubMed:7545958, ECO:0000269|PubMed:7573035, ECO:0000269|PubMed:7757088, ECO:0000269|PubMed:7887409, ECO:0000269|PubMed:7967473, ECO:0000269|PubMed:8032855, ECO:0000269|PubMed:8504306, ECO:0000269|PubMed:8664900, ECO:0000269|PubMed:8844217, ECO:0000269|PubMed:9671272}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Enzyme RegulationPyruvate dehydrogenase activity is inhibited by phosphorylation of PDHA1; it is reactivated by dephosphorylation. {ECO:0000269|PubMed:17474719, ECO:0000269|PubMed:19081061, ECO:0000269|PubMed:7782287}.
FunctionThe pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle. {ECO:0000269|PubMed:19081061, ECO:0000269|PubMed:7782287}.
PtmAcetylation alters the phosphorylation pattern. Deacetylated by SIRT3 (By similarity). {ECO:0000250}.
PtmPhosphorylation at Ser-232, Ser-293 and Ser-300 by PDK family kinases inactivates the enzyme; for this phosphorylation at a single site is sufficient. Dephosphorylation at all three sites, i.e. at Ser-232, Ser-293 and Ser-300, is required for reactivation. {ECO:0000269|PubMed:11486000, ECO:0000269|PubMed:17474719, ECO:0000269|PubMed:19081061, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:21406692}.
Sequence CautionSequence=AAA60055.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=AAB59581.1; Type=Frameshift; Positions=106, 175; Evidence={ECO:0000305};
Subcellular LocationMitochondrion matrix.
SubunitHeterotetramer of two PDHA1 and two PDHB subunits. The heterotetramer interacts with DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules. {ECO:0000269|PubMed:12651851, ECO:0000269|PubMed:14638692, ECO:0000269|PubMed:19081061}.
Tissue SpecificityUbiquitous.
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