Oxidation of succinate and the control of the citric acid cycle in the mitochondria of guinea-pig liver, mammary gland and kidney

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Abstract
Several con-ditions that control the rate of the oxidation of succinate by mitochondria from guinea-pig liver, mammary gland and kidney were investigated in studies of the kinetics of oxygen uptake and analyses of the interconver-sion of succinate, fumarate, malate and oxaloacetate. Kinetic studies of oxygen uptake revealed that in intact liver mitochondria the rate-determining step of the oxidation of succinate is the rate of phosphory-lation of ADP to ATP, whereas in mammary-gland mitochondria the oxidation of succinate is controlled by the rate of removal of oxaloacetate. The overall rate of the removal of oxaloacetate added to liver mitochondria was not affected by a variety of conditions such as the simultaneous oxidation of succinate, or the addition of ADP or 2,4-dinitrophenol. During oxidative phosphorylation of ADP the addition of oxaloacetate inhibited the oxidation of succinate only to a limited extent, but, on disruption of the energy supply by the addition of 2,4-dinitrophenol, oxaloacetate completely inhibited the oxidation of succinate. Mammary-gland mitochondria metabolize oxaloacetate more slowly than do liver mitochondria, and in this system the oxidation of succinate is more readily inhibited by oxaloacetate. The time-course of the inhibition of the oxidation of succinate by the addition of oxaloacetate and 2,4-dinitrophenol, as well as the stimulation of respiration on the addition of oxaloacetate to mitochondria in "state 4", indicates that there is an energy requirement for the local removal of oxaloacetate in the vicinity of the succinate-oxidase sites.