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Journal of Lipid Research, Vol 36, 2433-2443, Copyright © 1995 by Lipid Research, Inc.
SA Moore, E Hurt, E Yoder, H Sprecher and AA Spector
The purpose of this study was to determine whether the formation of
docosahexaenoic acid in human cells occurs through a pathway that involves
24-carbon n-3 fatty acid intermediates and retroconversion. Normal human
skin fibroblasts synthesized radiolabeled docosahexaenoic acid from
[1-(14)C]18:3n-3, [3-(14)C]22:5n-3, [3-(14)C]24:5n-3, and [3-
(14)C]24:6n-3. The amount of docosahexaenoate formed was reduced in
fibroblasts defective in peroxisomal biogenesis, by 90-100% in Zellweger's
syndrome and by 50-75% in infantile Refsum's disease. Fatty acid elongation
and desaturation were intact in these mutant cells. No decrease in
radiolabeled docosahexaenoic acid production occurred in mutant fibroblasts
defective in peroxisomal alpha-oxidation or mitochondrial beta-oxidation,
or in normal fibroblasts treated with methyl palmoxirate to inhibit
mitochondrial beta-oxidation. Therefore, the retroconversion step in
docosahexaenoic acid formation occurs through peroxisomal beta-oxidation in
normal human cells. These results demonstrate that the pathway for
docosahexaenoic acid synthesis in human cells involves 24-carbon
intermediates. The limited ability to synthesize docosahexaenoic acid may
underlie some of the pathology that occurs in genetic diseases involving
peroxisomal beta-oxidation.
ARTICLES
Docosahexaenoic acid synthesis in human skin fibroblasts involves peroxisomal retroconversion of tetracosahexaenoic acid
Department of Pathology, University of Iowa, Iowa City 52242, USA.
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