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* Departments of Clinical Chemistry and Pediatrics, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands
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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