An enzymatic approach to lactate production in human skeletal muscle during exercise

Purpose: This paper examines the production of lactate in human skeletal muscle over a range of power outputs (35-250% (V) over dotO(2max)) from an enzymatic flux point of view. The conversion of pyruvate and NADH to lactate and NAD in the cytoplasm of muscle cells is catalyzed by the near-equilibrium enzyme lactate dehydrogenase (LDH). As flux through LDH is increased by its substrates, pyruvate and NADH, the factors governing the production of these substrates will largely dictate how much lactate is produced at any exercise power output. In an attempt to understand lactate production, flux rates through the enzymes that regulate glycogenolysis/glycolysis, the transfer of cytoplasmic reducing equivalents into the mitochondria, and the various fates of pyruvate have been measured or estimated. Results: At low power outputs, the rates of pyruvate and NADH production in the cytoplasm are low, and pyruvate dehydrogenase (PDH) and the shuttle system enzymes (SS) metabolize the majority of these substrates, resulting in little or no lactate production. At higher power outputs (65, 90, and 250% (V) over dotO(2max)), the mismatch between the ATP demand and aerobic ATP provision at the onset of exercise increases as a function of intensity, resulting in increasing accumulations of the glycogenolytic/glycolytic activators (free ADP, AMP, and P-i). The resulting glycolytic flux, and NADH and pyruvate production, is progressively greater than can be handled by the SS and PDH, and lactate is produced at increasing rates. Lactate production during the onset of exercise and 10 min of sustained aerobic exercise, may be a function of adjustments in the delivery of O-2 to the muscles, adjustments in the activation of the aerobic ATP producing metabolic pathways and/or substantial glycogenolytic/glycolytic flux through a mass action effect.