Effects of perfusate leucine concentration on the metabolism of valine by the isolated rat hindquarter

Rates of oxidation of valine and release of alpha-ketoisovaleric acid by hindquarters from rats fed a 9% casein diet were measured at intervals over 90 minutes. The hindquarters were perfused with medium containing between 0.03 and 10 mmol/L L-leucine; concentrations of valine and isoleucine were kept constant at 0.2 and 0.1 mmol/L, respectively. The rate of oxidation of [1-14C]valine increased two to threefold when the perfusate contained 0.8 or 1.0 mmol/L leucine but was depressed by 50% when the leucine concentration was 10 mmol/L. The rate of release of alpha-ketoisovaleric acid from the hindquarter was affected little by perfusate leucine concentrations up to 1.0 mmol/L, but release was depressed when perfusate leucine concentration was increased to 10 mmol/L. The rate of release of alpha-ketoisocaproic acid increased with increasing perfusate leucine concentration, as did intracellular alpha-ketoisocaproic acid and leucine concentrations. These results indicate that valine oxidation by the isolated perfused hindquarter is stimulated by a high perfusate leucine concentration (1.0 mmol/L), suggesting that this response contributes to the depressed plasma and tissue valine pools of rats fed a high-leucine diet. An excessively high concentration of leucine (10 mmol/L) suppresses valine oxidation, presumably by competing with valine for transmination or transport.