J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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A more recent version of this article appeared on October 1, 2003

Papers In Press, published online ahead of print August 1, 2003
J. Lipid Res., doi:10.1194/jlr.M300223-JLR200
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Submitted on May 27, 2003
Revised on July 17, 2003
Accepted on July 17, 2003

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

Sacha Ferdinandusse, Simone Denis, Georges Dacremont, and Ronald J. A. Wanders

Lab. Genetic Metabolic Diseases, Academic Medical Center, Amsterdam 1100 DE

Corresponding Author: s.ferdinandusse{at}amc.uva.nl

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 [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 as fast as 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, 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 endoplasmic reticulum where it is incorporated into membrane lipids.


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