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

Purpose: This paper examines the production of lactate in human skeletal mu scle over a range of power outputs (35-250% (V) over dotO(2max)) from an en zymatic 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-equilibri um 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 e xercise power output. In an attempt to understand lactate production, flux rates through the enzymes that regulate glycogenolysis/glycolysis, the tran sfer of cytoplasmic reducing equivalents into the mitochondria, and the var ious fates of pyruvate have been measured or estimated. Results: At low pow er outputs, the rates of pyruvate and NADH production in the cytoplasm are low, and pyruvate dehydrogenase (PDH) and the shuttle system enzymes (SS) m etabolize the majority of these substrates, resulting in little or no lacta te 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 on set of exercise increases as a function of intensity, resulting in increasi ng 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 lacta te is produced at increasing rates. Lactate production during the onset of exercise and 10 min of sustained aerobic exercise, may be a function of adj ustments in the delivery of O-2 to the muscles, adjustments in the activati on of the aerobic ATP producing metabolic pathways and/or substantial glyco genolytic/glycolytic flux through a mass action effect.