PDC (pyruvate dehydrogenase complex) catalyses the oxidative decarboxylation of pyruvate, linking glycolysis to the tricarboxylic acid cycle. Regulation of PDC determines and reflects substrate preference and is critical to the ‘glucose–fatty acid cycle’, a concept of reciprocal regulation of lipid and glucose oxidation to maintain glucose homoeostasis developed by Philip Randle. Mammalian PDC activity is inactivated by phosphorylation by the PDKs (pyruvate dehydrogenase kinases). PDK inhibition by pyruvate facilitates PDC activation, favouring glucose oxidation and malonyl-CoA formation: the latter suppresses LCFA (long-chain fatty acid) oxidation. PDK activation by the high mitochondrial acetyl-CoA/CoA and NADH/NAD+ concentration ratios that reflect high rates of LCFA oxidation causes blockade of glucose oxidation. Complementing glucose homoeostasis in health, fuel allostasis, i.e. adaptation to maintain homoeostasis, is an essential component of the response to chronic changes in glycaemia and lipidaemia in insulin resistance. We develop the concept that the PDKs act as tissue homoeostats and suggest that long-term modulation of expression of individual PDKs, particularly PDK4, is an essential component of allostasis to maintain homoeostasis. We also describe the intracellular signals that govern the expression of the various PDK isoforms, including the roles of the peroxisome proliferator-activated receptors and lipids, as effectors within the context of allostasis.
Skip Nav Destination
Article navigation
December 2003
- PDF Icon PDF LinkFront Matter
Conference Article|
December 01 2003
Regulation of pyruvate dehydrogenase complex activity by reversible phosphorylation
M.J. Holness;
M.J. Holness
Department of Diabetes and Metabolic Medicine, Division of General and Developmental Medicine, Medical Sciences Building, Bart's and the London, Queen Mary's School of Medicine and Dentistry, University of London, Mile End Road, London E1 4NS, U.K.
Search for other works by this author on:
M.C. Sugden
M.C. Sugden
1
Department of Diabetes and Metabolic Medicine, Division of General and Developmental Medicine, Medical Sciences Building, Bart's and the London, Queen Mary's School of Medicine and Dentistry, University of London, Mile End Road, London E1 4NS, U.K.
1To whom correspondence should be addressed (e-mail m.c.sugden@qmul.ac.uk).
Search for other works by this author on:
Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2003 Biochemical Society
2003
Biochem Soc Trans (2003) 31 (6): 1143–1151.
Citation
M.J. Holness, M.C. Sugden; Regulation of pyruvate dehydrogenase complex activity by reversible phosphorylation. Biochem Soc Trans 1 December 2003; 31 (6): 1143–1151. doi: https://doi.org/10.1042/bst0311143
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.