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1 Human Biology & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
2 The Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
3 The Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; The August Krogh Institute, University of Copenhagen, Copenhagen, Denmark
* To whom correspondence should be addressed. E-mail: marinamo{at}cancerboard.ab.ca.
During prolonged exercise, carbohydrate oxidation may result from decreased pyruvate production and increased fatty acid supply, and ultimately lead to reduced pyruvate dehydrogenase (PDH) activity. Pyruvate also interacts with the amino acids alanine, glutamine and glutamate whereby the decline in pyruvate production could affect TCA cycle flux as well as gluconeogenesis. To enhance our understanding of these interactions, we studied the time-course of changes in substrate utilization in 6 male subjects who cycled at 44±1%VO2peak (mean±SE) until exhaustion (EXH: 3h 23min±11min). Femoral arterial and venous blood, blood flow measurements and muscle samples were obtained hourly during exercise and recovery (3h). Carbohydrate oxidation peaked at 30 min of exercise and subsequently decreased for the remainder of the exercise bout (p<0.05). PDH activity peaked at 2h of exercise whereas pyruvate production peaked at 1 hour of exercise and was reduced (~30%) thereafter suggesting that pyruvate availability primarily accounted for reduced carbohydrate oxidation. Increased FFA uptake (p<0.05) was also associated with decreasing PDH activity (p<0.05) and increased PDH kinase4 mRNA (p<0.05) during exercise and recovery. At 1h of exercise, pyruvate production was greatest and was closely linked to glutamate, which was the predominant amino acid taken up during exercise and recovery. Alanine and glutamine were also associated with pyruvate metabolism and they comprised ~68% of total amino acid release during exercise and recovery. Thus, reduced pyruvate production was primarily associated with reduced carbohydrate oxidation, while the greatest production of pyruvate was related to glutamate, glutamine and alanine metabolism in early exercise.
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