Regulation of glycogen phosphorylase and PDH during exercise in human skeletal muscle during hypoxia

The present study examined the acute effects of hypoxia on the regulation o f skeletal muscle metabolism at rest and during 15 min of submaximal exerci se. Subjects exercised on two occasions for 15 min at 55% of their normoxic maximal oxygen uptake while breathing 11% O-2 (hypoxia) or room air (normo xia). Muscle biopsies were taken at rest and after 1 and 15 min of exercise . At rest, no effects on muscle metabolism were observed in response to hyp oxia. In the 1st min of exercise, glycogenolysis was significantly greater in hypoxia compared with normoxia. This small difference in glycogenolysis was associated with a tendency toward a greater concentration of substrate, free P-i, in hypoxia compared with normoxia. Pyruvate dehydrogenase activi ty (PDHa) was lower in hypoxia at 1 min compared with normoxia, resulting i n a reduced rate of pyruvate oxidation and a greater lactate accumulation. During the last 14 min of exercise, glycogenolysis was greater in hypoxia d espite a lower mole fraction of phosphorylase a. The greater glycogenolytic rate was maintained posttransformationally through significantly higher fr ee [AMP] and [P-i]. At the end of exercise, PDHa was greater in hypoxia com pared with normoxia, contributing to a greater rate of pyruvate oxidation. Because of the higher glycogenolytic rate in hypoxia, the rate of pyruvate production continued to exceed the rate of pyruvate oxidation, resulting in significant lactate accumulation in hypoxia compared with no further lacta te accumulation in normoxia. Hence, the elevated lactate production associa ted with hypoxia at the same absolute workload could in part be explained b y the effects of hypoxia on the activities of the rate-limiting enzymes, ph osphorylase and PDH, which regulate the rates of pyruvate production and py ruvate oxidation, respectively.