Some effects of propionate upon acetate metabolism in animal tissue slices.

A number of instances of inhibitory effects of propionic acid on metabolic reactions have been reported. Grafflin & Green (1948) found that the oxidation of acetate by washed rabbit-kidney particles ('cyclophorase') was inhibited by propionate, which itself was not oxidized. The oxygen uptake of sheep-rumen epithelial tissue was shown (Pennington, 1954) to be markedly depressed by propionate in a medium without bicarbonate, but was increased by propionate in a medium buffered with bicarbonate-carbon dioxide. It was suggested that, in the absence of carbon dioxide, the metabolism of propionyl-coenzyme A was blocked and that coenzyme A, which would normally be available for the metabolism of endogenous substances, was immobilized as propionyl-coenzyme A. Propionate suppresses ketone-body formation by rumen epithelium from pyruvate and decreases slightly the uptake of pyruvate (Pennington & Sutherland, 1956a). Lang & Bassler (1953) found that propionate inhibited the oxygen uptake of particle preparations from rabbit liver" and kidney in the presence oflow levels of succinate; the formation of acetoacetate from acetate by the liver preparations was depressed also. These effects were attributed to effective competition by propionate for coenzyme A. It has been established that propionate inhibits the growth ofmany micro-organisms (see Heseltine, 1952). Hill (1952) showed that the suppression of growth of Streptococcus faecal8 by propionate could be reversed by acetate. He suggested that, by combining with coenzyme A, propionate interferes with the oxidative decarboxylation of pyruvate to acetate. The ruminant liver normally metabolizes considerable quantities of propionic acid, formed in the rumen. Consequently, any inhibitory effects of propionate may be of considerable physiological importance to this class of animals. The present studies were concerned with possible effects of propionate on the metabolism of acetate, which is present in relatively high concentration in the blood of ruminants. Most of the experiments described were carried out, for convenience, with rat liver. It subsequently became evident, however, that there was a marked species difference in the magnitude of the effects of propionate.