Regulation of protein metabolism in relation to adequacy of intake.

Abstract

The daily flux of amino acids in the body is extensive. Protein synthesis is estimated to be 300 g daily in an adult man. This requires uptake and release of 150 g essential amino acids, yet the dietary requirement for essential amino acids in only 6 g. This indicates extensive and efficient recycling of essential amino acids released by protein breakdown. The catabolism of essential amino acids by the liver is sensitively regulated in relation to requirements. A study of availability of tryptophan to rats receiving various levels of tryptophan in the diet shows that plasma tryptophan increases only when intake exceeds requirements and at these higher levels of intake tryptophan oxygenase activity in the liver becomes increased shortly after meals. In addition, the carbohydrate content of the diet causes tryptophan to become deposited in the free amino acid pool of muscle through an insulin-dependent mechanism. Dietary carbohydrate also effects plasma tryptophan due to a fall in the plasma level of non-esterified fatty acids which compete with tryptophan for binding sites on serum albumin. Consequently, after carbohydrate the proportion of plasma tryptophan bound to serum albumin increases, so that there is less nonbound tryptophan in the plasma. The metabolic significance of this has yet to be demonstrated. Finally, protein metabolism in skeletal muscle exhibits considerable efficiency of reutilization of essential amino acids, since the main products passing into the blood are alanine and glutamine. It has been shown that 3-methylhistidine present in muscle protein in not reutilized for synthesis of protein and that its excretion in the urine can provide a useful index of muscle catabolism. In prolonged starvation of adults or protein deficiency in children, output of 3-methylhistidine is much reduced, suggesting an adaptive reduction in muscle protein catabolism. It is emphasized that, because of its function in monitoring dietary amino acid intake, liver protein metabolism responds rapidly to changes in protein intake and in consequence protein deficiency causes early depletion, whereas muscle protein undergoes depletion later and is subject to adaptive processes that restrict the loss.