Propionic acid metabolism in mouse liver slices.

Odd carbon fatty acids are considered to be oxidized in tissue by successive fl oxidation in much the same way that even carbon members of the series are (14). The terminal S-carbon unit has been investigated to some extent. Atchley (5) demonstrated propionic acid as an end-product in the oxidation of valeric acid by a rabbit enzyme system. Studies on malonate inhibition with odd carbon fatty acids (6) indicated a small amount of conversion of the 3-carbon residue to a 2-carbon unit of the type CH3-CO. Siegel and Lorber (7) found that Valerie acid gave much the same metabolic patterns in glycogen in the whole rat, as would appear with a mixture of propionic acid and acetic acid. The intermediates in p oxidation have been investigated (8, 9) with enzyme systems. The results indicate comparable rates of oxidation for a-~ unsaturated acids and the corresponding saturated acids and formation of identical products. P-Keto and ,&hydroxy acids were oxidized to some extent, but there are indications that phosphorylated analogues are the actual intermediates. The fate of the end-product, 3-carbon segment or propionic acid itself is still somewhat in doubt,. Lorber e2 al. ruled out, the possibility of p oxidation to malonate (10) in an isotopic experiment. Distribution of activity in this experiment showed an a-/3 randomization by the time the oxidized propionic acid substrate appeared in liver glycogen in the intact rat. A comparable experiment with lactate (11) did not give complete a-0 randomization, and from these results it was suggested that the oxidation of propionate either does not follow a direct path, propionate-acrylatelactate-pyruvate, or else has a fast side equilibration, with symmetrical Krebs cycle intermediates. In working with isolated rabbit enzymes, Huennekens et al. (12) have supported the theory for a direct pathway, advancing the sequence propionate-acrylate+lactate-n-lactate-pyruvate, etc., with an cu-hydroxy racemase necessaryfor complete oxidation. The direct, path of oxidation had been suggested in the case of mold (13) and muscle tissue (14) previously. In the present experiments with liver slices we wished to show, by