Although the fatty acid oxidation scheme works neatly for even- numbered chain lengths, it can't work completely for fatty acids that contain an odd number of carbons. β-oxidation of these compounds leads to
propionyl-CoA and acetyl-CoA, rather than to two acetyl-CoA at the final step. The propionyl-CoA is not a substrate for the TCA cycle or other simple pathways. Propionyl-CoA undergoes a
carboxylation reaction to form
methylmalonyl-CoA. This reaction requires biotin as a cofactor, and is similar to an essential step in fatty acid biosynthesis. Methylmalonyl-CoA is then isomerized by an epimerase and then by
methylmalonyl-CoA mutase—an enzyme that uses Vitamin B12 as a cofactor—to form succinyl-CoA, which is a TCA-cycle intermediate.
Branched-chain fatty acids present a problem of a similar kind. For example, phytanic acid, found in animal milk, can't be oxidized directly by β-oxidation because the addition of water is a problem at the branched β-carbon.
The first step in the digestion of this compound is the oxidation of the χ
carbon by molecular oxygen. Then the original carboxyl group is removed as CO2, leaving a shorter chain. This chain can now be accommodated by the β-oxidation reactions, because the new β-carbon now lacks a methyl group. (Note that the branch points yield propionyl-CoA, and must enter the TCA cycle through methylmalonate.
Fatty Acid Oxidation
Lipid Biosynthesis
