Inactivation of PDC by phosphorylation of PDC E1 alpha component Activation of PDC by dephosphorylation of phospho-E1 alpha component PathwayStep2153 PathwayStep2152 Regulation of pyruvate dehydrogenase (PDH) complex Authored: Gopinathrao, G, 2007-11-26 20:29:38 GENE ONTOLOGYGO:0010510 Pubmed12676647 Reactome Database ID Release 43204174 Reactome, http://www.reactome.org ReactomeREACT_12528 Reviewed: D'Eustachio, P, 2008-01-11 20:49:08 The mitochondrial pyruvate dehydrogenase (PDH) complex catalyzes the oxidative decarboxylation of pyruvate, linking glycolysis to the tricarboxylic acid cycle and fatty acid synthesis. PDH inactivation is crucial for glucose conservation when glucose is scarce, while adequate PDH activity is required to allow both ATP and fatty acid production from glucose. The mechanisms that control human PDH activity include its phosphorylation (inactivation) by pyruvate dehydrogenase kinases (PDK 1-4) and its dephosphorylation (activation, reactivation) by pyruvate dehydrogenase phosphate phosphatases (PDP 1 and 2). Isoform-specific differences in kinetic parameters, regulation, and phosphorylation site specificity of the PDKs introduce variations in the regulation of PDC activity in differing endocrine and metabolic states (Sugden and Holness 2003).