A low carbohydrate diet increases human skeletal muscle pyruvate dehydrogenase activity

To characterize human skeletal muscle enzymatic adaptation to a low carbohydrate (CHO) diet, subjects consumed a diet consisting of 5% CHO, 62% fat, and 33% protein for 6 d compared to their normal diet (48% CHO, 34% fat, and 18% protein). Biopsies were taken from the vastus lateralis prior to and following 3 and 6 d on a low CHO diet. Intact mitochondria were extracted from fresh muscle and were analyzed for pyruvate dehydrogenase (PDH) kinase and carnitine palmitoyl transferase I activites, and mitochondrial ATP production rate (using CHO and fat substrates). β-Hydroxyacyl CoA dehydrogenase and citrate synthase activities were measured on total muscle homogenates PDH kinase was calculated as the absolute value of the pseudo-first order rate constant of the inactivation of pyruvate dehydrogenase (PDH) in the presence of 0.3 mM Mg²⁺-ATP. PDH kinase increased dramatically from 0.10 ± 0.02 min^-1 to 0.35 ± 0.09 min^-1 at 3 d, and 0.49 ± 0.06 min^-1 after 6 d. Activities for all other enzymes were not altered by the low CHO diet. Therefore, severe deficiency of dietary CHO causes a rapid 3 to 5-fold increase in PDH kinase activity, thereby facilitating down-regulation of PDH activity and CHO metabolism. However, the expected increase in activities of enzymes involved in fatty acid oxidation did not occur.