title: Docosahexaenoic acid synthesis in human skin fibroblasts involves peroxisomal retroconversion of tetracosahexaenoic acid.
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.
authors.affiliation: Department of Pathology, University of Iowa, Iowa City 52242, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Moore
authors.forename: E
authors.initials: E
authors.lastname: Hurt
authors.forename: E
authors.initials: E
authors.lastname: Yoder
authors.forename: H
authors.initials: H
authors.lastname: Sprecher
authors.forename: A A
authors.initials: AA
authors.lastname: Spector
mesh_terms: D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008830:Microbodies / Q000378:metabolism*; D009154:Mutation; D010084:Oxidation-Reduction; D012016:Reference Values; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D015211:Zellweger Syndrome / Q000378:metabolism / Q000473:pathology; D017962:alpha-Linolenic Acid / Q000378:metabolism
chemical_list: D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; C099831:tetracosahexaenoic acid; C099830:tetracosapentaenoic acid; C026219:docosapentaenoic acid