Fuel metabolism is highly regulated to ensure adequate energy for cellular function. The contribution of the major metabolic fuels - glucose, lactate and fatty acids (FAs) - often reflects their circulating levels. In addition, regulatory crosstalk and fuel-induced hormone secretion ensures appropriate and co-ordinate fuel utilization. Because its activity can either determine or reflect fuel preference (carbohydrate versus fat), the pyruvate dehydrogenase complex (PDC) occupies a pivotal position in fuel cross-talk. Active PDC permits glucose oxidation and allows the formation of mitochondrially derived intermediates (e.g. malonyl-CoA and citrate) that reflect fuel abundance. FA oxidation suppresses PDC activity. PDC inactivation by phosphorylation is catalysed by pyruvate dehydrogenase kinases (PDKs) 1–4, which are regulated differentially by metabolite effectors. Most tissues contain at least two and often three of the PDK isoforms. We develop the hypothesis that PDK4 is a ‘lipid status’-responsive PDK isoform facilitating FA oxidation and signalling through citrate formation. Substrate interactions at the level of gene transcription extend glucose-FA interactions to the longer term. We discuss potential targets for substrate-mediated transcriptional regulation in relation to selective PDK isoform expression and the influence of altered PDK isoform expression in fuel sensing, selection and utilization.
Skip Nav Destination
Article navigation
May 2001
- Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkAdvertising
Conference Article|
May 01 2001
Fuel-sensing mechanisms integrating lipid and carbohydrate utilization
M. C. Sugden;
M. C. Sugden
1
1Department of Diabetes and Metabolic Medicine, St Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary, University of London, London E1 4NS, U.K.
1To whom correspondence should be addressed (e-mail m.c.sugden@qmw.ac.uk)
Search for other works by this author on:
K. Bulmer;
K. Bulmer
1Department of Diabetes and Metabolic Medicine, St Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary, University of London, London E1 4NS, U.K.
Search for other works by this author on:
M.J. Holness
M.J. Holness
1Department of Diabetes and Metabolic Medicine, St Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary, University of London, London E1 4NS, U.K.
Search for other works by this author on:
Biochem Soc Trans (2001) 29 (2): 272–278.
Article history
Received:
November 13 2000
Citation
M. C. Sugden, K. Bulmer, M.J. Holness; Fuel-sensing mechanisms integrating lipid and carbohydrate utilization. Biochem Soc Trans 1 May 2001; 29 (2): 272–278. doi: https://doi.org/10.1042/bst0290272
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.