Special problems: oxidation of fatty acids with an odd number of carbon atoms

The eventual product of oxidation of a fatty acid chain with an odd number of carbon atoms is the three-carbon thioester propionyl CoA. This must then be further metabolized by a special series of reactions that begins with the carboxylation of propionyl CoA. This reaction, catalyzed by propionyl CoA carboxylase [EC 6.4.1.3] , is similar to the acetyl CoA carboxylase reaction of fatty acid synthesis or the pyruvate carboxylase reaction, and takes place with the assistance of a biotin cofactor and the input of energy from ATP.

The next two reactions are isomerizations. The product of the propionyl CoA carboxylase reaction is methylmalonyl CoA, a molecule in which carbon 2 is a stereocenter. The (S) stereoisomer is converted to the (R) form by methylmalonyl CoA racemase [EC 5.1.99.1].

Methylmalonyl CoA mutase [EC 5.4.99.2] catalyzes an unusual carbon skeleton rearrangement (see figure below). The mechanism is thought to be based on production of a radical initiated when the Co-C bond in the 5'-deoxyadenosylcobalamin prosthetic group undergoes homolytic cleavage. This type of mechanism is uncommon in biochemical reactions - most reactions in metabolism involve heterolytic bond breaking. The reaction converting (R)-methylmalonyl CoA into succinyl CoA is one of two mammalian metabolic reactions known to be dependent on 5'-deoxyadenosylcobalamin.