Effect of intraarterial infusion of the ketoanalogue of leucine on amino acid release by forearm muscle

Abstract

α-Ketoanalogues of most essential amino acids can be converted to the corresponding amino acids in man and appear to be useful dietary supplements in protein-intolerant patients. Recently, the branchedchain amino acids, especially leucine, have been found to promote protein synthesis in isolated muscle. The present studies were designed to assess the capacity of skeletal muscle to aminate the keto-analogue of leucine and determine if the metabolism of the ketoacid promotes protein synthesis. Six normal postabsorptive males received a 30-min brachial intraarterial infusion of ketoleucine (34.4 μmoles/min). Changes in ipsilateral muscle balance were estimated from whole blood concentrations and flow for 1 hr. Brachial arterial blood ketoleucine concentration increased by an average of 1.02 m M. In a single passage across forearm muscle, 52% of the ketoacid was extracted. Leucine was the only amino acid released in increased amounts, accounting for 31% of ketoleucine extracted. The remainder was apparently oxidized. No one donor capable of supplying all the nitrogen needed for leucine production could be identified, but significant reductions in the release of alanine, glycine, and histidine, and changes from release to uptake of valine and isoleucine, suggest possible contributions from these amino acids. Glutamine-asparagine release did not change. Lysine, tyrosine, and phenylalanine balances were also unchanged, suggesting no anabolic effect of ketoleucine on muscle protein under these conditions. The results demonstrate rapid transamination and utilization of ketoleucine by skeletal muscle in postabsorptive man.