Pyruvate dehydrogenase

Pyruvate dehydrogenase (PDH) is an enzyme that is part of the citric acid cycle. It catalyzes the reaction that transforms pyruvate into acetyl-CoA, a process called pyruvate decarboxylation. PDH activity is inhibited by pyruvate dehydrogenase kinase (PDK).

PDH activity is controlled by multiple different factors, including but not limited to:


 * PDH kinases (PDKs), that inhibit activity of PDH enzymes
 * PDH phosphatases that yank away PDH’s phosphate group so it does not function properly
 * Sirtuin 4 (SIRT4), which is also an inhibitor for PDH
 * PDK1, 2, 3, and 4
 * A shift in these or their expression means a shift towards higher glucose, lower pyruvate, lower Acetyl Co-A, and fewer energy-rich molecules produced in the cell to do work.

In ME/CFS
A large study by Fluge and Mella of 200 patients meeting the Canadian Consensus Criteria and 102 controls found a pattern of amino acids that suggested functional impairment of pyruvate dehydrogenase (PDH), supported by increased mRNA expression of the inhibitory PDH kinases 1, 2, and 4; sirtuin 4; and PPARδ in peripheral blood mononuclear cells from both sexes.

Learn more

 * Fluge, Mella, and Armstrong: More Support for Disordered Metabolism in ME Patients, #MEAction, December 23, 2016