PDHA1 encodes pyruvate dehydrogenase E1-α, a subcomponent of the pyruvate dehydrogenase complex (PDC), a large mitochondrial multi-enzyme complex. The PDC exhibits 3 main enzymatic functions (E1-3) and is required in the Krebs cycle for irreversibly converting pyruvate into acetyl-coA. E1, the structural core of the PDC, comprises a heterotetramer that consists of 2 PDHα and 2 PDHβ subunits. The PDHα subunit harbors the active oxidation site where pyruvate is decarboxylated; the released acetyl group is accepted by dihydrolipoamide acetyltransferase, which is the second main enzyme component (E2) in the PDC.
PDHA1 dysfunction causes pyruvate dehydrogenase E1-α deficiency, the most common disorder attributed to pyruvate dehydrogenase complex deficiency and X-linked Leigh syndrome. The disorders are biochemically characterized by lactic acidosis, the result of large quantities of unused pyruvate being converted into lactate.