Metabolism of branched-chain amino acids in altered nutrition

Plasma concentrations of the branched-chain amino acids (leucine, isoleucine, and valine) are more prominently affected than the concentrations of other amino acids by changes in dietary—caloric, protein, fat, and carbohydrate—intake in man. For example, within a day of starvation or protein deprivation, there are increases or decreases, respectively, in concentrations of these amino acids in the plasma of healthy human volunteers. The cellular mechanisms of these changes have been investigated in rats, since the changes in the plasma branched-chain amino acid concentrations in response to the previously stated dietary alterations are similar to those found in man. Among the tissues studied (liver, skeletal muscle, heart, kidney, and intestine) only liver and the skeletal muscle exhibit changes in branched-chain amino acid concentrations in response to dietary alteration. Changes in plasma concentrations appear to reflect more intimately those of the muscle than the liver. After 8 days of starvation, there is a 25% decrease in the muscle protein, but after 8 days of protein deprivation, there is no significant change in the muscle mass. Increases in concentrations of branched-chain amino acids in the muscle are much smaller than the amounts of these amino acids lost as protein constituents from the muscle during fasting. Changes in tissue transport, transamination, oxidation, or metabolic conversions of branched-chain amino acids are not responsible for the alteration in pool sizes of free branched-chain amino acids in tissues. It is concluded that increased muscle protein breakdown, which provides substrates for enhanced gluconeogenesis in the liver and enhanced branched-chain amino acid oxidation in the muscle, is the major mechanism of hyperbranched-chain aminoacidemia in starvation. On the other hand, the principal factors in the development of hypobranched-chain aminoacidemia during protein deprivation are absence of exogenous amino acids as well as curtailed muscle protein breakdown.