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Regulation of leucine and alpha keto iso caproate metabolism in skeletal muscle


, : Regulation of leucine and alpha keto iso caproate metabolism in skeletal muscle. Journal of Biological Chemistry 253(22): 8126-8133

Leucine catabolism by the perfused rat hindquarter was studied by measuring transamination of leucine and the formation and oxidative decarboxylation of .alpha.-ketoisocaproic acid. The perfusate contained 0.10 or 0.50 mM [114C]leucine, all other amino acids at approximately reported rat plasma concentrations and 5.5 mM glucose. Release of a-ketoisocaproic acid by the hindquarter was immediate. By 60 min, .alpha.-ketoisocaproic acid always accounted for 20-30% of the total circulating leucine carbon ([leucine] + [.alpha.-ketoisocaproic acid]). In nonrecirculating perfusions, .alpha.-ketoisocaproic acid release represented 46% of the leucine undergoing transamination. In perfusions with insulin, when [1-14C].alpha.-ketoisocaproic acid was substituted for leucine, the major fate of .alpha.-ketoisocaproic acid was transamination to leucine rather than oxidation. Using a nonrecirculating perfusion with 0.50 mM leucine, the apparent rate of oxidative decarboxylation of [1-14C].alpha.-ketoisocaproic acid was 7.4 nmol .cntdot. g-1 muscle per min (54% of the rate of transamination). With an initial leucine concentration of 0.50 mM in a recirculating perfusion system, .alpha.-ketoisocaproic acid decarboxylation averaged 5.19 nmol .cntdot. g-1 muscle per min. With an initial leucine concentration of 0.10 mM, decarboxylation increased continuously but reached a rate of only 0.88 nmol .cntdot. g-1 muscle per min at the end of 2 h. Insulin addition significantly decreased the rate of decarboxylation and reduced leucine transamination. In the recirculating system with insulin, increasing the initial leucine concentration from 0.10-0.50 mM stimulated net leucine uptake 8- to 9-fold and enhanced oxidation 5- to 15-fold, depending on the time interval. Raising the initial leucine concentration or adding insulin, or both, stimulated net valine and isoleucine uptake by the perfused hindquarter but decreased release of their respective .alpha.-keto acids, .alpha.-ketoisovaleric acid and .alpha.-keto-.beta.-methylvaleric acid. Amino acid concentrations and the hormonal state of the animal influence the extent to which branched-chain .alpha.-keto acids will be oxidized by or released from muscle.

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Accession: 006288982

PMID: 711739

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