Degradation of malonic acid by rat tissues.

In past years, malonate has been extensively used in mammalian systems in vitro as an inhibitor of the citric acid cycle with very little attention given its metabolism per se. Lifson and Stolen (1) demonstrated the conversion of V-labeled malonate to carbon dioxide in the intact mouse. Later, Lee and Lifson (2) found that the administration to rats of doses of U3-labeled malonate at an inhibiting concentration resulted in the excretion of C13labeled succinate in the urine. These findings indicate that malonate is an active metabolic substrate in the intact rat. Recently, Wick, Wolfe, and Nakada (3), using eviscerated-nephrectomized rabbits, showed that malonate is a poor inhibitor in vivo of acetate oxidation. Further investigation indicated that an inhibitory intracellular concentration of malonate was not obtained, due to the slow entry of malonate into the cells from the extracellular compartment and the concomitant removal of intracellular malonate by oxidation (3). Wolfe, Ivler, and Rittenberg (4) and Hayaishi (5) have reported independently on the enzymatic decarboxylation of malonate by purified enzyme systems from Pseudomonas jfuorescens. These workers have shown that malonate is activated in the presence of adenosine triphosphatel and coenzyme A to form malonyl coenzyme A, which is subsequently decarboxylated to acetyl CoA and carbon dioxide. The present study was undertaken to investigate the metabolism in vitro of malonate by rat tissues and to test for the possible occurrence of the microbial mechanism in the degradation of malonate by mammalian tissues.