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[edit | edit source]
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[edit | edit source]
- Fluge, Mella, and Armstrong: More Support for Disordered Metabolism in ME Patients, #MEAction, December 23, 2016
References[edit | edit source]
- Arenas, J.; Huertas, R.; Campos, Y.; Díaz, A. E.; Villalón, J. M.; Vilas, E. (Mar 14, 1994). "Effects of L-carnitine on the pyruvate dehydrogenase complex and carnitine palmitoyl transferase activities in muscle of endurance athletes". FEBS letters. 341 (1): 91–93. doi:10.1016/0014-5793(94)80246-7. ISSN 0014-5793. PMID 8137928.
- Tronstad, Karl J.; Dahl, Olav; Ueland, Per M.; Helgeland, Lars; Sommerfelt, Kristian; McCann, Adrian; Schäfer, Christoph; Bohnen, Louis M. L. J.; Baranowska, Katarzyna A. (Jan 3, 2017). "Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome". JCI Insight. 1 (21). doi:10.1172/jci.insight.89376. ISSN 0021-9738.
enzyme - a substance produced by a living organism which acts as a catalyst to bring about a specific biochemical reaction.