Propionate inhibition of succinate:CoA ligase (GDP) and the citric acid cycle in mitochondria.

Propionate inhibits oxygen consumption by rat liver mitochondria when glutamate, alpha-ketaglutarate, and succinate are substrates. Carnitine prevents this effect. The pattern of inhibition of 14CO2 release from metabolic intermediates indicates citric acid cycle inhibition between succinate:coenzyme A (CoA) ligase (GDP) and malate dehydrogenase. Propionyl CoA is synthesized from propionate in mitochondria. Propionyl CoA is a potent inhibitor of succinate:CoA ligase with positive cooperativity and half half-maximal inhibition at 2 X 10(-4) M propionyl CoA.