Isotope studies on the metabolism of valine.

Previous information on the catabolism of valine has been obtained by taking advantage, for the most part, of the gluconeogenic property of valine and using glucose as an indicator of its intermediary metabolism. Thus, Rose et al. (1) reported that valine and a-ketoisovaleric acid have similar gluconeogenic effects, both contributing 3 of their carbon atoms to glucose formation in phlorizinized dogs. Previously, Ringer and coworkers (2) had observed that isobutyric acid, the decarboxylation product of a-ketoisovaleric acid, also furnishes 3 carbon atoms to the formation of glucose. Studies in which isotopically labeled valine was administered to fasted rats, and the glycogen isolated and degraded, confirmed the formation of a S-carbon intermediate, which was presumed to be propionic acid (3). The investigation described in the present paper was undertaken in order to obtain direct evidence regarding the nature of the intermediates of valine oxidation. Using nn-valine-4 ,4’-C14, we have been able to isolate and identify labeled a-ketoisovaleric, isobutyric, and propionic acids by chromatographic means. Evidence has also been obtained which indicates that carbon atoms 3, 4, and 4’ of valine give rise to propionic acid and that the conversion of isobutyric acid to propionic acid proceeds by way of P-hydroxyisobutyric acid and the removal of its carboxyl group.’