The Formation of Glutamine and Alanine in Skeletal Muscle

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Abstract The formation of glutamine and alanine by skeletal muscle was studied in the isolated perfused rat hindquarter. When perfused with a semisynthetic medium, the hindquarter released the full spectrum of amino acids with glutamine and alanine accounting for 50 % of the amino acid appearing in the perfusate. The pattern of amino acid release was similar to that of the human forearm. Fasting for 48 hours caused a 55 % increase in the efflux of alanine but had little effect on the efflux of most other amino acids. Diabetes caused an increase in the efflux of nearly all amino acids; however, alanine and glutamine still accounted for half of the amino acid released. Perfusion with 10 mm leucine, lysine, and histidine increased the rates of release of both glutamine and alanine. This could not be explained by a washout of glutamine or alanine from tissue, suggesting that these amino acids were formed de novo. The release of alanine and glutamine was also increased by perfusion with 10 mm valine, glycine, or proline. Methionine sulfoximine, an irreversible inhibitor of glutamine synthetase, decreased the leucine-induced increase in glutamine efflux by 50 %. Alanine release was increased by the addition of lactate or lactate and pyruvate to the perfusate. Insulin had little effect on the release of glutamine and alanine by hindquarters of fed and fasted rats, but it depressed the very large release of these amino acids in diabetic rats. Glucagon had no effect on the release of either amino acid, nor did exercise induced by sciatic nerve stimulation at rates of 2 and 5 per s. The data indicate that the high rates of glutamine and alanine release by muscle can be accounted for by their synthesis within the muscle cell. They also indicate that muscle synthesizes glutamine, at least in part via glutamine synthetase, and it forms alanine via glutamic-pyruvic aminotransferase.