Succinate accumulation in vivo following injection of malonate.

Among the factors involved in the accumulation of citrate by a tissue following the injection of fluoroacetate in viva is the ability of the tissue to convert precursors into 4-carbon acids (1). An indirect measure of the importance of this conversion was reported in a recent study (2) in which the Krebs cycle was blocked both by fluoroacetate and malonate, but in this study concurrent analyses for succinate were not attempted. Recently developed chromatographic techniques (3) have made it possible to determine not only the concentration of succinate, the metabolite accumulated, but also the concentration of malonate, the inhibitor, in tissue extracts following the injection of malonate. Previous studies on the effects of malonate in wivo have dealt with the metabolism of CY-malonate (4-6) and the effects of malonate on components of blood and urine (7-10). In the present study, the optimal conditions for the accumulation of succinate in tissues in viva were defined, and the rate of excretion of succinate, citrate, and malonate in the urine was determined.