Pyruvate dehydrogenase

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Pyruvate dehydrogenase or 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.

PDH activity can be increased by supplementing with L-carnitine.[1]

ME/CFS[edit | edit source]

A large study by Øystein Fluge and Olav 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.[2]

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References[edit | edit source]

  1. Arenas, J.; Huertas, R.; Campos, Y.; Díaz, A.E.; Villalón, J.M.; Vilas, E. (March 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.
  2. Tronstad, Karl J.; Dahl, Olav; Ueland, Per M.; Helgeland, Lars; Sommerfelt, Kristian; McCann, Adrian; Schäfer, Christoph; Bohnen, Louis M. L.J.; Baranowska, Katarzyna A. (January 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.