Regulation of pyruvate dehydrogenase via PDK and PDP

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Reactome-Recon connection

The connection was chosen from the Reactome-Recon lists: proteins of the Recon2 metabolic reconstruction that take part in Reactome signalling processes. The PDH complex is in the lists through the Reactome processes PDK isozymes phosphorylate PDHC subunit E1 (R-HSA-203946) and PDP1,2 dephosphorylate p-lipo-PDH (R-HSA-204169).

Description

The pyruvate dehydrogenase complex (PDH) converts pyruvate, CoA and NAD+ into acetyl-CoA, CO2 and NADH, the irreversible step that decides whether carbon from glucose is oxidised in mitochondria. Pyruvate dehydrogenase kinases (PDK1-4) inactivate PDH by phosphorylating its PDHA1 subunit, and the phosphatases PDP1 and PDP2 reactivate it. The products acetyl-CoA and NADH inhibit the complex directly and also stimulate PDK, while pyruvate inhibits PDK. Ca2+ stimulates PDP1, linking PDH activation to muscle contraction. The drug dichloroacetate inhibits PDK and lowers blood lactate in congenital lactic acidosis.

References

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Contributors

Alexander Mazein1

Affiliations
  1. 1Department of Cancer Research, Luxembourg Institute of Health, Strassen, Luxembourg