Fatty acids with an odd number of carbons are found in the lipids of plants and some marine organisms. Many ruminant animals form a large amount of 3-carbon propionate during the fermentation of carbohydrates in the rumen. Long-chain fatty acids with an odd number of carbon atoms are found particularly in ruminant fat and milk.
Chains with an odd-number of carbons are oxidized in the same manner as even-numbered chains, but the final products are propionyl-CoA and acetyl-CoA.
Propionyl-CoA is first carboxylated using a bicarbonate ion into a D-stereoisomer of methylmalonyl-CoA. This reaction involves a biotin co-factor, ATP and the enzyme propionyl-CoA carboxylase. The bicarbonate ion's carbon is added to the middle carbon of propionyl-CoA, forming a D-methylmalonyl-CoA. However, the D-conformation is enzymatically converted into the L-conformation by methylmalonyl-CoA epimerase. It then undergoes intramolecular rearrangement, which is catalyzed by methylmalonyl-CoA mutase (requiring B as a coenzyme) to form succinyl-CoA. The succinyl-CoA formed then enters the citric acid cycle.
However, whereas acetyl-CoA enters the citric acid cycle by condensing with an existing molecule of oxaloacetate, succinyl-CoA enters the cycle as a principal in its own right. Thus, the succinate just adds to the population of circulating molecules in the cycle and undergoes no net metabolization while in it. When this infusion of citric acid cycle intermediates exceeds cataplerotic demand (such as for aspartate or glutamate synthesis), some of them can be extracted to the gluconeogenesis pathway, in the liver and kidneys, through phosphoenolpyruvate carboxykinase, and converted to free glucose.