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Originally published In Press as doi:10.1194/jlr.M300223-JLR200 on August 1, 2003

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Journal of Lipid Research, Vol. 44, 1992-1997, October 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

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

Sacha Ferdinandusse1,*, Simone Denis*, Georges Dacremont{dagger} and Ronald J. A. Wanders*

* Departments of Clinical Chemistry and Pediatrics, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands
{dagger} Department of Pediatrics, University of Ghent, Ghent, Belgium

1 To whom correspondence should be addressed. e-mail: 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 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 ß-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.

Abbreviations: CACT, carnitine acyl-carnitine translocator; D-BP, D-bifunctional protein; DHA, docosahexaenoic acid; MTP, mitochondrial trifunctional protein; PBD, peroxisome biogenesis disorder; TE, thioesterase

Supplementary key words peroxisomes • ß-oxidation • docosahexaenoic acid • thioesterase • acyl-CoA oxidase


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