Anaplerotic processes in human skeletal muscle during brief dynamic exercise

1. This study examined changes in tricarboxylic acid cycle intermediates (TCAIs) in human skeletal muscle during 5 min of dynamic knee extensor exercise (approximately 80% of maximum workload) and following 2 min of recovery. 2. The sum of the seven measured TCAIs (sigma TCAIs) increased from 1.10 +/- 0.08 mmol (kg dry weight)-1 at rest to 3.12 +/- 0.24, 3.86 +/- 0.35 and 4.33 +/- 0.30 mmol (kg dry weight)-1 after 1, 3 and 5 min of exercise, respectively (P < or = 0.05): The sigma TCAIs after 2 min of recovery (3.74 +/- 0.43 mmol (kg dry weight)-1) was not different compared with 5 min of exercise. 3. The rapid increase in sigma TCAIs during exercise was primarily mediated by large changes in succinate, malate and fumarate. These three intermediates accounted for > 90% of the net increase in sigma TCAIs during the first minute of contraction. 4. Intramuscular alanine increased after 1 min of exercise by an amount similar to the increase in the sigma TCAIs (2.33 mmol (kg dry weight)-1) (P < or = 0.05). Intramuscular pyruvate was also higher (P < or = 0.05) during exercise, while intramuscular glutamate decreased by approximately 50% within 1 min and remained low despite an uptake from the circulation (P < or = 0.05). 5. The calculated net release plus estimated muscle accumulation of ammonia after 1 min of exercise (approximately 60 mumol (kg wet weight)-1) indicated that only a minor portion of the increase in sigma TCAIs could have been mediated through the purine nucleotide cycle and/or glutamate dehydrogenase reaction. 6. It is concluded that the close temporal relationship between the increase in sigma TCAIs and changes in glutamate, alanine and pyruvate metabolism suggests that the alanine aminotransferase reaction is the most important anaplerotic process during the initial minutes of contraction in human skeletal muscle.