Abstract |
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.
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Authors | S A Moore, E Hurt, E Yoder, H Sprecher, A A Spector |
Journal | Journal of lipid research
(J Lipid Res)
Vol. 36
Issue 11
Pg. 2433-43
(Nov 1995)
ISSN: 0022-2275 [Print] United States |
PMID | 8656081
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Fatty Acids, Omega-3
- Fatty Acids, Unsaturated
- alpha-Linolenic Acid
- Docosahexaenoic Acids
- tetracosahexaenoic acid
- tetracosapentaenoic acid
- docosapentaenoic acid
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Topics |
- Cells, Cultured
- Docosahexaenoic Acids
(metabolism)
- Fatty Acids, Omega-3
(metabolism)
- Fatty Acids, Unsaturated
(metabolism)
- Fibroblasts
(metabolism)
- Humans
- Microbodies
(metabolism)
- Mutation
- Oxidation-Reduction
- Reference Values
- Skin
(cytology, metabolism)
- Zellweger Syndrome
(metabolism, pathology)
- alpha-Linolenic Acid
(metabolism)
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