Oxidation of Fatty Acids:- Complete Oxidation of Odd-Number Fatty Acids Requires Three Extra Reactions
Although most naturally occurring lipids contain fatty acids with an even number of carbon atoms, fatty acids with an odd number of carbons are common in the lipids of many plants and some marine organisms. Cattle and other ruminant animals form large amounts of the three-carbon propionate (CH3-CH2-COO-) during fer mentation of carbohydrates in the rumen. The propionate is absorbed into the blood and oxidized by the liver and other tissues. And small quantities of propionate are added as a mold inhibitor to some breads and cereals, thus entering the human diet. Long-chain odd-number fatty acids are oxidized in the same pathway as the even-number acids, beginning at the carboxyl end of the chain. However, the substrate for the last pass through the β-oxidation sequence is a fatty acyl–CoA with a five-carbon fatty acid. When this is oxidized and cleaved, the products are acetyl-CoA and propionyl-CoA. The acetyl-CoA can be oxidized in the citric acid cycle, of course, but propionyl-CoA enters a different pathway involving three enzymes. Propionyl-CoA is first carboxylated to form the D stereoisomer of methylmalonyl-CoA (Fig. 17–11) by propionyl-CoA carboxylase, which contains the co factor biotin. In this enzymatic reaction, as in the pyruvate carboxylase reaction, CO2 (or its hydrated ion, HCO3-) is activated by attachment to biotin before its transfer to the substrate, in this case the propionate moiety. Formation of the carboxybiotin intermediate requires energy, which is provided by the cleavage of ATP to ADP and Pi. The D-methylmalonyl CoA thus formed is enzymatically epimerized to its L stereoisomer by methylmalonyl-CoA epimerase (Fig. 17–11). The L-methylmalonyl-CoA then undergoes an intramolecular rearrangement to form succinyl-CoA, which can enter the citric acid cycle. This rearrange ment is catalyzed by methylmalonyl-CoA mutase, which requires as its coenzyme 5-deoxyadenosyl cobalamin, or coenzyme B12, which is derived from vitamin B12 (cobalamin).
FIGURE 17–11 Oxidation of propionyl-CoA produced by oxidation of odd-number fatty acids. The sequence involves the carboxylation of propionyl-CoA to D-methylmalonyl-CoA and conversion of the latter to succinyl-CoA. This conversion requires epimerization of D- to L-methylmalonyl-CoA, followed by a remarkable reaction in which substituents on adjacent carbon atoms exchange positions.
