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Am J Physiol Endocrinol Metab 275: E980-E986, 1998;
0193-1849/98 $5.00
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Vol. 275, Issue 6, E980-E986, December 1998

Human skeletal muscle pyruvate dehydrogenase kinase activity increases after a low-carbohydrate diet

Sandra J. Peters, Timothy A. St. Amand, Richard A. Howlett, George J. F. Heigenhauser, and Lawrence L. Spriet

Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario N1G 2W1; and Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada

To characterize human skeletal muscle enzymatic adaptation to a low-carbohydrate, high-fat, and high-protein diet (LCD), subjects consumed a eucaloric diet consisting of 5% of the total energy intake from carbohydrate, 63% from fat, and 33% from protein for 6 days compared with their normal diet (52% carbohydrate, 33% fat, and 14% protein). Biopsies were taken from the vastus lateralis before and after 3 and 6 days on a LCD. Intact mitochondria were extracted from fresh muscle and analyzed for pyruvate dehydrogenase (PDH) kinase, total PDH, and carnitine palmitoyltransferase I activities and mitochondrial ATP production rate (using carbohydrate and fat substrates). beta -Hydroxyacyl CoA dehydrogenase, active PDH (PDHa), and citrate synthase activities were also measured on whole muscle homogenates. PDH kinase (PDHK) was calculated as the absolute value of the apparent first-order rate constant of the inactivation of PDH in the presence of 0.3 mM Mg2+-ATP. PDHK increased dramatically from 0.10 ± 0.02 min-1 to 0.35 ± 0.09 min-1 at 3 days and 0.49 ± 0.06 min-1 after 6 days. Resting PDHa activity decreased from 0.63 ± 0.17 to 0.17 ± 0.04 mmol · min-1 · kg-1 after 6 days on the diet, whereas total PDH activity did not change. Activities for all other enzymes were unaltered by the LCD. In summary, severe deficiency of dietary carbohydrate combined with a twofold increase in dietary fat and protein caused a rapid three- to fivefold increase in PDHK activity in human skeletal muscle. The increased PDHK activity downregulated the amount of PDH in its active form at rest and decreased carbohydrate metabolism. However, an increase in the activities of enzymes involved in fatty acid oxidation did not occur.

carbohydrate metabolism; beta -hydroxyacyl coenzyme A dehydrogenase; carnitine palmitoyltransferase I; citrate synthase; mitochondrial ATP production


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