Regulation of skeletal muscle glycogen phosphorylase and PDH during maximal intermittent exercise

The time course for the activation of glycogen phosphorylase (Phos) and pyr uvate dehydrogenase (PDH) and their allosteric regulators was determined in human skeletal muscle during repeated bouts of maximal exercise. Six subje cts completed three 30-s bouts of maximal isokinetic cycling separated by 4 -min recovery periods. Muscle biopsies were taken at rest and at 6, 15, and 30 s of exercise during bouts 1 and 3. Phos was rapidly activated within t he first 6 s of bout 1 from 12% at rest to 47% at 6 s. The activation of PD H increased from 14% at rest to 48% at 6 s and 95% at 15 s of bout 1. Phos reverted back to basal values at the end of the first bout, whereas PDH rem ained fully activated. In contrast, in the third bout, PDH was 42% at rest and was activated more rapidly and was nearly completely activated by 6 s, whereas Phos remained at basal levels (range 14-20%). Lactate accumulation was marked in the first bout and increased progressively from 2.7 to 76.1 m mol/kg dry wt with no further increase in bout 3. Glycogen utilization was also marked in the first bout and was negligible in bout 3. The rapid activ ation of Phos and slower activation of PDH in bout 1 was probably due to Ca 2+ release from the sarcoplasmic reticulum. Lactate accumulation appeared t o be due to an imbalance of the relative activities of Phos and PDH. The in crease in Hf concentration may have served to reduce pyruvate production by inhibiting Phos transformation and may have simultaneously activated PDH i n the third bout such that there was a better matching between pyruvate pro duction and oxidation and minimal lactate accumulation. As each bout progre ssed and with successive bouts, there was a decreasing ability to stimulate substrate phosphorylation through phosphocreatine hydrolysis and glycolysi s and a shift toward greater reliance on oxidative phosphorylation.