Effect of pent-4-enoic acid, propionic acid and other short-chain fatty acids on citrulline synthesis in rat liver mitochondria

Abstract

The effect of pent-4-enoic acid, propionic acid and several other short-chain fatty acids on citrulline synthesis in rat liver mitochondria was studied. Pent-4-enoate at 1 mM inhibited mitochondrial citrulline synthesis by about 80-90%. Pent-4-enoate inhibits citrulline synthesis by interfering with some aspect of mitochondrial energy metabolism. This results in impairment of mitochondrial ornithine uptake or depletion of mitochondrial ATP, which, in turn, impairs carbamoyl phosphate synthesis or both. Pent-4-enoate has no effect on citrulline synthesis supported by succinate or exogenous ATP. Pent-4-enoate lowers the medium plus mitochondrial ATP concentration. When glutamate is the oxidizable substrate, pent-4-enoate decreases the carbamoyl phosphate concentration in mitochondria incubated without ornithine to minimize citrulline synthesis and impairs the mitochondrial uptake of ornithine, but it has neither effect when succinate is the oxidizable substrate. Propionate, butyrate and crotonate also inhibit mitochondrial citrulline synthesis, but much less than pent-4-enoate. Acetate, pentanoate, pent-2-enoate, hexanoate, octanoate, isovalerate, tiglylate and .alpha.-methylbutyrate have little or no effect on mitochondrial citrulline synthesis.