Abstract
Several different processes involved in the metabolic fate of docosahexaenoic acid (DHA, C22:6n-3) and its precursor in the biosynthesis route, C24:6n-3, were studied. In cultured skin fibroblasts, the oxidation rate of [1-14C] 24:6n-3 was 2.7 times higher than for [1-14C]22:6n-3, whereas [1-14C]22:6n-3 was incorporated 7 times faster into different lipid classes than was [1-14C]24:6n-3. When determining the peroxisomal acyl-CoA oxidase activity, similar specific activities for C22:6(n-3)-CoA and C24:6(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 C22:6(n-3)-CoA was hydrolyzed 1.7 times faster than C24:6(n-3)-CoA. These results imply that the preferred metabolic fate of C24:6(n-3)-CoA, after its synthesis in the endoplasmic reticulum (ER), is to move to the peroxisome, where it is beta-oxidized, producing C22:6(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.
Highlights
Several different processes involved in the metabolic fate of docosahexaenoic acid (DHA, C22:6n-3) and its precursor in the biosynthesis route, C24:6n-3, were studied
It was found that a 24-carbon n-3 fatty acid is synthesized, which is desaturated at position 6 to produce C24:6n-3, followed by one round of -oxidation in the peroxisome, with C22:6n-3 as the final product [5,6,7]
Because Docosahexaenoic acid (DHA) is the most abundant n-3 polyunsaturated fatty acids (PUFAs) in most tissues and is found at the sn-2 position of phospholipids, DHA has to move back to the endoplasmic reticulum (ER) to be acylated into phospholipids instead of being further -oxidized in the peroxisome
Summary
Several different processes involved in the metabolic fate of docosahexaenoic acid (DHA, C22:6n-3) and its precursor in the biosynthesis route, C24:6n-3, were studied. It has been hypothesized that competition between peroxisomal -oxidation and ER-associated acylation reactions plays a role in this regulation and in regulating membrane lipid fatty acid composition [8, 9]. We have measured -oxidation with both substrates in fibroblasts from patients with different peroxisomal and mitochondrial fatty acid oxidation defects and, for comparison, we performed studies of incorporation into different lipid classes with these substrates.
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