Effect of experimental liver disease on the utilization for protein synthesis of orally administered alpha-ketoisocaproate.

The incorporation of orally administered 1-14C-alpha-ketoisocaproate into the leucine of proteins in rats was compared with the incorporation of [3H]leucine itself administered simultaneously and expressed as a ratio, R. This ratio in whole body protein has been shown to be approximately equal to the nutritional efficiency of alpha-ketoisocaproate as a dietary substitute for leucine. In normal rats on a 14% protein diet, R in whole body protein (0.30 +/- 0.01) and in the protein of various organs was the same whether the isotopes were given by single injection or 6-hr constant infusion. Thus, both techniques yield the same time-independent parameter, R, which measures the relative efficiency of alpha-ketoisocaproate as a substitute for leucine. R varied between organs as follows: liver (0.22 +/- 0.01) less than kidney less than heart less than salivary gland less than brain less than muscle (0.42 +/- 0.01). In rats with galactosamine-induced acute liver failure (Group I), carbon tetrachloride-induced cirrhosis (Group II), or portal-systemic shunts (Group III), whole body protein R and R in the protein of organs other than the liver was generally increased compared with controls, as was R in circulating IgG in Group III; R in liver protein was unchanged (Groups II and III) or slightly lower than controls (Group I). Thus, severe liver disease and portal-systemic shunting both increase the utilization of alpha-ketoisocaproate for synthesis of protein in the body as a whole and in most organs. In the liver, however, alpha-ketoisocaproate utilization for protein synthesis is unaffected or slightly reduced.