This pathway depicts the metabolism of propionic acid. Propionic acid in mammals typically arises from the production of the acid by gut or skin microflora. Propionic acid producing bacteria (Propionibacterium sp.) are particularly common in sweat glands of mammals. After entering a cell, the propionic acid (propanoate) then enters the mitochondria where it is converted into propanol adenylate (or propionyl adenylate or propionyl-AMP) via propionyl-CoA synthetase and acetyl-CoA synthetase. The propionyl adenylate then is converted into propionyl coenzyme A (propionyl-CoA) via the same pair of enzymes. Propionyl-CoA is a relatively common compound that can also arise from the metabolic breakdown of fatty acids containing odd numbers of carbon atoms. Propionyl-CoA is also known to arise from the breakdown of some amino acids. Since propanoate has three carbons, propionyl-CoA cannot directly enter the beta-oxidation cycle (which requires two carbons from acetyl-CoA). Therefore, in most vertebrates, propionyl-CoA is carboxylated into D-methylmalonyl-CoA via propionyl-CoA carboxylase. The resulting compound is isomerized into L-methylmalonyl-CoA via methylmalonyl-CoA epimerase. A vitamin B12-dependent enzyme, called methylmalonyl CoA mutase catalyzes the rearrangement of L-methylmalonyl-CoA to succinyl-CoA, which is an intermediate of the citric acid cycle. Also depicted in this pathway is another propionic acid homolog called hydroxypropanoic acid (hydroxypropionate). This compound is also produced by bacteria and imported into cells. Hydroxypropionate can be converted into 3-hydroxypropionyl-CoA. This compound can be either enzymatically converted to acryloyl-CoA and then to propionyl-CoA or it can spontaneously convert to malonyl-CoA. Malonyl-CoA can convert into acetyl-CoA (via acetyl-CoA carboxylase in the cytoplasm or malonyl carboxylase in the mitochondria) whereupon it may enter a variety of pathways. In a rare genetic metabolic disorder called propionic acidemia, propionate acts as a metabolic toxin in liver cells by accumulating in the liver mitochondria as propionyl-CoA and its derivative methylcitrate. Both propionyl-CoA and methylcitrate are known TCA inhibitors. Glial cells are particularly susceptible to propionyl-CoA accumulation. In fact, when propionate is infused into rat brains and take up by the glial cells, it leads to behavioural changes that resemble autism (PMID: 16950524).

Propanoate Metabolism References