Propionate inhibits oxygen consumption by rat liver mitochondria when glutamate, α-ketoglutarate, 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-maximal inhibition at 2 x 10-4 M propionyl CoA. Inhibition of oxidative phosphorylation and the citric acid cycle may produce the Reye's-like syndrome which occurs in propionic acidemia and possibly related organic acid or mitochondrial disorders. Mitochondrial acyl coenzyme A may be increased in these patients and respond favorably to carnitine therapy.
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health