The present study examined the acute effects of
hypoxia on the regulation of skeletal muscle metabolism at rest and during 15 min of submaximal exercise. 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 (normoxia). 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
hypoxia. 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 activity (PDH(a)) was lower in
hypoxia at 1 min compared with normoxia, resulting in a reduced rate of
pyruvate oxidation and a greater
lactate accumulation. During the last 14 min of exercise, glycogenolysis was greater in
hypoxia despite a lower mole fraction of
phosphorylase a. The greater glycogenolytic rate was maintained posttransformationally through significantly higher free [
AMP] and [P(i)]. At the end of exercise, PDH(a) was greater in
hypoxia compared 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
lactate accumulation in normoxia. Hence, the elevated
lactate production associated with
hypoxia at the same absolute workload could in part be explained by the effects of
hypoxia on the activities of the rate-limiting
enzymes,
phosphorylase and PDH, which regulate the rates of
pyruvate production and
pyruvate oxidation, respectively.