Propanoic Acid - Metabolism

Metabolism

The metabolism of propanoic acid begins with its conversion to propionyl coenzyme A (propionyl-CoA), the usual first step in the metabolism of carboxylic acids. Since propanoic acid has three carbons, propionyl-CoA cannot directly enter either beta oxidation or the citric acid cycles. In most vertebrates, propionyl-CoA is carboxylated to D-methylmalonyl-CoA, which is isomerised to L-methylmalonyl-CoA. A vitamin B12-dependent enzyme catalyzes rearrangement of L-methylmalonyl-CoA to succinyl-CoA, which is an intermediate of the citric acid cycle and can be readily incorporated there.

In propanoic acidemia, a rare inherited genetic disorder, propionate acts as a metabolic toxin in liver cells by accumulating in mitochondria as propionyl-CoA and its derivative, methylcitrate, two tricarboxylic acid cycle inhibitors. Propanoate is metabolized oxidatively by glia, which suggests astrocytic vulnerability in propanoic acidemia when intramitochondrial propionyl-CoA may accumulate. Propanoic acidemia may alter both neuronal and glial gene expression by affecting histone acetylation. When propanoic acid is infused directly into rodents brains it produces reversible behavior (e.g., hyperactivity, dystonia, social impairment, perseveration) and brain (e.g., innate neuroinflammation, glutathione depletion) changes that may be used as a means to model autism in rats.