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Free access | 10.1172/JCI107048
1Clayton Laboratories for Study of Control of Cell Function in Health and Disease, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
Find articles by Pozefsky, T. in: JCI | PubMed | Google Scholar
1Clayton Laboratories for Study of Control of Cell Function in Health and Disease, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
Find articles by Tancredi, R. in: JCI | PubMed | Google Scholar
Published September 1, 1972 - More info
Postabsorptive release of alanine from forearm skeletal muscle is large relative to other amino acids, suggesting new synthesis by transamination of pyruvate. This hypothesis was tested and the pathway quantified in six subjects, each given two 30 min intrabrachial arterial pyruvate infusions. The first (12 μmoles/min) supplied approximately that amount of pyruvate produced endogenously by glycolysis in resting muscle. The second (36 μmoles/min) approximated endogenous pyruvate production by glycolysis during moderate exercise. Changes in balance across forearm tissues of pyruvate, glucose, lactate, and amino acids were measured. The time-course of pyruvate equilibration across fore-arm muscles was detailed in three additional subjects.
The two infusions increased arterial pyruvate from 64 to 674 and 1776 μmoles/liter respectively. Muscle consumed 72% of the exogenous pyruvate during both infusions. Outputs of lactate and alanine increased, accounting respectively for 30.3 and 6.7% of the pyruvate at the low infusion rate, and 17.1 and 3.8% at the high rate. The remaining pyruvate probably was oxidized. Muscle release of valine, isoleucine, and leucine decreased during the high dose infusion. Additionally, adipose tissue plus skin released more alanine and lactate during the high dose infusion. Other metabolies were unchanged.
Thus, both muscle and adipose tissue plus skin synthesize alanine from pyruvate. Lactate production considerably exceeds that of alanine. In muscle, increased availability of intracellular pyruvate serving as a nitrogen acceptor may facilitate branched chain amino acid oxidation. Muscle consumption of infused pyruvate is rapid, and detailed studies of its equilibration suggest that passage across the muscle cell membrane is rate limiting.