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PDHA1 a mitochondrial matrix enzyme that catalyzes the oxidative decarboxylation of pyruvate, producing acetyl-CoA and CO2. A key enzyme in controlling the balance between lipid and glucose oxidation depending on substrate availability. The pyruvate dehydrogenase (PDH) holoenzyme is a multi-enzyme complex (PDHC) that contains 20-30 copies of pyruvate decarboxylase tetramers (2 alpha:2 beta)(E1), 60 copies of dihydrolipoamide acetyltransferase (E2), six homodimers of dihydrolipoamide dehydrogenase (E3), plus E3 binding proteins. The activity of PDH is tightly regulated by phosphorylation. The phosphorylation of at least one of three specific serine residues in E1 subunit by PDHK inactivates the PDHC, while dephosphorylation by PDP restores its activity. Sites 1, 2, and 3 of PDHA1 are S293, S300, and S232, respectively. Four PDHK isoenzymes have been described, each with different site specificity: all four phosphorylate sites 1 and 2 but at different rates; for site 1 PDHK2 >PDHK4 >PDHK1 >PDHK3; for site 2, PDHK3> PDHK4 > PDHK2 > PDHK1. Only PDHK1 phosphorylates site 3. PDHA1 deficiency is the most common enzyme defect in patients with primary lactic acidosis. Note: This description may include information from UniProtKB.
Protein type: Amino Acid Metabolism - valine, leucine and isoleucine biosynthesis; Carbohydrate Metabolism - butanoate; Carbohydrate Metabolism - citrate (TCA) cycle; Carbohydrate Metabolism - glycolysis and gluconeogenesis; Carbohydrate Metabolism - pyruvate; EC; Mitochondrial; Oxidoreductase
Chromosomal Location of Human Ortholog: Xp22.12
Cellular Component: mitochondrial matrix; mitochondrion; myelin sheath; nucleolus; nucleus; pyruvate dehydrogenase complex
Molecular Function: protein binding; pyruvate dehydrogenase (acetyl-transferring) activity; pyruvate dehydrogenase (NAD+) activity; pyruvate dehydrogenase activity
Biological Process: acetyl-CoA biosynthetic process from pyruvate; cellular nitrogen compound metabolic process; glucose metabolic process; mitochondrial acetyl-CoA biosynthetic process from pyruvate; pyruvate metabolic process; regulation of acetyl-CoA biosynthetic process from pyruvate; tricarboxylic acid cycle
Disease: Pyruvate Dehydrogenase E1-alpha Deficiency
Reference #:  P08559 (UniProtKB)
Alt. Names/Synonyms: ODPA; PDHA; PDHA1; PDHCE1A; PDHE1-A type I; PHE1A; pyruvate dehydrogenase (lipoamide) alpha 1; pyruvate dehydrogenase complex, E1-alpha polypeptide 1; pyruvate dehydrogenase E1 alpha 1; Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
Gene Symbols: PDHA1
Molecular weight: 43,296 Da
Basal Isoelectric point: 8.35  Predict pI for various phosphorylation states
CST Pathways:  Warburg Effect
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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