Stimulation of the glycine cleavage system by short-chain fatty acids in isolated rat liver mitochondria.

The effect of short-chain fatty acids on glycine catabolism by the glycine cleavage system was investigated in isolated rat liver mitochondria. Metabolic flux through the glycine cleavage system was monitored by measuring the production of 14CO2 from [1-14C]glycine. Propionate, butyrate, pentanoate, and octanoate, and to a lesser extent acetate, all significantly stimulated 14CO2 production from [1-14C]glycine by isolated rat liver mitochondria maintained in state 4. Concomitant with the stimulation of 14CO2 production was a decrease in the measured intramitochondrial content of NADPH which we have previously demonstrated correlates with the metabolic flux through the glycine cleavage system [Hampson, R.K., Barron, L.L., & Olson, M.S. (1983) J. Biol. Chem. 258, 2993-2999]. The propionate-mediated stimulation of mitochondrial 14CO2 production from [1-14C]glycine was not diminished by the addition of L-carnitine but was abrogated nearly completely by the addition of oligomycin. Incubation of the mitochondria with short-chain fatty acids evoked a large decrease in the measured intramitochondrial ATP content and a large increase in the AMP content. However, manipulation of the intramitochondrial adenine nucleotide profile demonstrated that no direct correlation existed between ATP, ADP, or AMP and 14CO2 production from [1-14C]glycine. These experimental results indicate that short-chain fatty acid oxidation causes the oxidation of the NADP(H) redox couple in isolated rat liver mitochondria, resulting in the stimulation of the metabolic flux through the glycine cleavage system.(ABSTRACT TRUNCATED AT 250 WORDS)