Studies on the metabolic fate of n-3 polyunsaturated fatty acids.
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.
Ferdinandusse
Sacha
S
Departments of Clinical Chemistry and Pediatrics, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. S.Ferdinandusse@amc.uva.nl
Denis
Simone
S
Dacremont
Georges
G
Wanders
Ronald J A
RJ
D042962:Acyl-CoA Oxidase / Q000378:metabolism; D000818:Animals; D002250:Carbon Radioisotopes; D002478:Cells, Cultured / Q000187:drug effects; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013869:Thiolester Hydrolases / Q000378:metabolism
D002250:Carbon Radioisotopes; D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D008563:Membrane Lipids; D004281:Docosahexaenoic Acids; D042962:Acyl-CoA Oxidase; D013869:Thiolester Hydrolases