Catabolism and synthesis of amino acids in skeletal muscle: their significance in monogastric mammals and ruminants

Abstract

The enhanced rate of synthesis and catabolism of amino acids in, and their release from, skeletal muscle, particularly during fasting, exercise and metabolic acidosis, highlight the integrative role of muscle in protein-energy metabolism. This review discusses aspects of such changes in muscles of monogastric mammals and ruminants. The glucose-alanine cycle, as it was originally proposed, has been well substantiated by studies using human and rat muscles. An alternative proposal, which suggested that other amino acids make a major contribution to the carbon skeleton of alanine synthesized in muscle, is less convincing, since some of the inhibitors and substrates used in relevant studies have been demonstrated to have multiple rather than specific effects. In the ruminant, the glucose-alanine cycle is quantitatively less significant than in human. The probable reason for this difference is the limited available pyruvate in ruminant muscle for transamination to alanine. This may be due to a lower carbon flux through the glycolytic pathway and/or to significant activity of the anaplerotic enzyme, pyruvate carboxylase. It is suggested that glutamine is the more important carrier of carbon and nitrogen out of skeletal muscle and that alanine may serve only as an ancillary vehicle to transport carbon and nitrogen when the availability of pyruvate for transamination in muscle is high. The more diverse role of glutamine (cf. alanine) in acid-base balance, as a respiratory fuel in the cells of the immune system and the epithelia of the small intestine, where it may also be converted to alanine for subsequent gluconeogenesis in the liver, is consistent with this suggestion.