page_title: Pyruvate dehydrogenase kinase
section_title: Regulation
hierarchical_section_title: Pyruvate dehydrogenase kinase / Regulation
caption_attribution_description: English: The fourth isozyme of pyruvate dehydrogenase kinase with a bound ADP molecule in the active site
context_page_description: Pyruvate dehydrogenase kinase is a kinase enzyme which acts to inactivate the enzyme pyruvate dehydrogenase by phosphorylating it using ATP.
  PDK thus participates in the regulation of the pyruvate dehydrogenase complex of which pyruvate dehydrogenase is the first component. Both PDK and the pyruvate dehydrogenase complex are located in the mitochondrial matrix of eukaryotes. The complex acts to convert pyruvate to acetyl-coA, which is then oxidized in the mitochondria to produce energy, in the citric acid cycle. By downregulating the activity of this complex, PDK will decrease the oxidation of pyruvate in mitochondria and increase the conversion of pyruvate to lactate in the cytosol.
  The opposite action of PDK, namely the dephosphorylation and activation of pyruvate dehydrogenase, is catalyzed by a phosphoprotein phosphatase called pyruvate dehydrogenase phosphatase.
context_section_description: Pyruvate dehydrogenase kinase is activated by ATP, NADH and acetyl-CoA. It is inhibited by ADP, NAD+, CoA-SH and pyruvate.
  Each isozyme responds to each of these factors slightly differently. NADH stimulates PDK1 activity by 20% and PDK2 activity by 30%. NADH with acetyl-CoA increases activity in these enzymes by 200% and 300% respectively. In similar conditions, PDK3 is unresponsive to NADH and inhibited by NADH with acetyl-CoA. PDK4 has a 200% activity increase with NADH, but adding acetyl-CoA does not increase activity further.
caption: PDK isozyme 4 with ADP bound in the active site. ADP has been shown to be a competitive inhibitor.[8]
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