Studies on the metabolic fate of n-3 polyunsaturated fatty acids.

ABSTRACT

Several different processes involved in the metabolic fate of docosahexaenoic acid (DHA, C226n-3) and its precursor in the biosynthesis route, C246n-3, were studied. In cultured skin fibroblasts, the oxidation rate of [1-14C] 246n-3 was 2.7 times higher than for [1-14C]226n-3, whereas [1-14C]226n-3 was incorporated 7 times faster into different lipid classes than was [1-14C]246n-3. When determining the peroxisomal acyl-CoA oxidase activity, similar specific activities for C226(n-3)-CoA and C246(n-3)-CoA were found in mouse kidney peroxisomes. Thioesterase activity was measured for both substrates in mouse kidney peroxisomes as well as mitochondria, and C226(n-3)-CoA was hydrolyzed 1.7 times faster than C246(n-3)-CoA. These results imply that the preferred metabolic fate of C246(n-3)-CoA, after its synthesis in the endoplasmic reticulum (ER), is to move to the peroxisome, where it is beta-oxidized, producing C226(n-3)-CoA. This DHA-CoA then preferentially moves back, probably as free fatty acid, to the ER, where it is incorporated into membrane lipids.