Role of muscle and liver in leucine catabolism in rats fed excessive leucine

It is thought that muscle and liver cooperate to dispose branched‐chain amino acids (BCAA) when their intake is above the requirement. We examined the effects of large excesses of leucine on the metabolism of BCAA in the muscle and liver. F344 male rats, 6 weeks of age, were fed diets containing additional leucine (0, 1.5, 5, 10, 15 and 30 % (w/w)) for 14 days. Plasma, liver and gastrocnemius muscle were harvested to quantify BCAA and their ketoacids. Dietary supplementation of leucine (1.5 to 10%) decreased valine and isoleucine concentrations indicating the activation of BCAA catabolism in these animals. Supplementation with very large amounts of leucine (15 to 30%) resulted in a significant rise in plasma leucine and increases in valine and isoleucine concentrations, indicating saturation in BCAA catabolism. Although muscular α‐ketoisocaproic acid (α‐KIC) concentrations elevated in parallel with plasma leucine, hepatic α‐KIC concentrations were kept at very low levels even when rats were fed excessive leucine. Branched‐chain ketoacid dehydrogenase (BCKDH), a rate limiting enzyme for BCAA catabolism, is localized predominantly to liver in rats, while liver lacks branched‐chain aminotransferase (BCAT) to produce the substrates of BCKDH. The results of this experiment suggested that, at extremely high leucine intakes, the transport of α‐KIC out of the muscle into the liver may be the rate limiting step in the leucine catabolism.