Estimation of the mitochondrial redox state in human skeletal muscle during exercise.
The mitochondrial redox (NAD+/NADH) state can be used as a reflection of oxygen availability within the mitochondrion. Previous studies using isolated muscle preparations suggest that active muscle is not hypoxic during lactate production, whereas experiments with humans come to the opposite conclusion. Six men exercised for 5 min at 75% maximal O2 consumption (VO2max) and then at 100% VO2max to exhaustion. Ammonia, oxoglutarate (alpha-ketoglutarate), and glutamate, as well as lactate, were measured in biopsies (vastus lateralis) taken at the end of each exercise. The three former metabolites were used to determine the mass action ratio of glutamate dehydrogenase and thus were used as an estimate of the mitochondrial redox state. Muscle lactate increased (P less than 0.05) to 14.5 and 24.5 mmol/kg wet wt after 75 and 100% VO2max, respectively. At both exercise intensities, muscle ammonia rose (P less than 0.05), glutamate fell (P less than 0.05) to only 30-35% of rest levels, and oxoglutarate declined (P less than 0.05). Despite the high levels of muscle lactate accumulation, the estimated mitochondrial redox rate rose 300% (P less than 0.05) in both exercise bouts. This response should increase the activity of key oxidative enzymes and promote increased VO2. Furthermore the data do not support the concept that muscle lactate is formed because of tissue hypoxia.
Graham
T E
TE
August Krogh Institute, University of Copenhagen, Denmark.
Saltin
B
B
D000328:Adult; D000641:Ammonia / Q000097:blood; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006801:Humans; D007656:Ketoglutaric Acids / Q000378:metabolism; D007773:Lactates / Q000097:blood / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D005082:Physical Exertion
D005971:Glutamates; D007656:Ketoglutaric Acids; D007773:Lactates; D009243:NAD; D019344:Lactic Acid; D018698:Glutamic Acid; D000641:Ammonia; D005969:Glutamate Dehydrogenase