Docosahexaenoic acid synthesis in human skin fibroblasts involves peroxisomal retroconversion of tetracosahexaenoic acid
1995; Elsevier BV; Volume: 36; Issue: 11 Linguagem: Inglês
10.1016/s0022-2275(20)39724-8
ISSN1539-7262
AutoresSteven A. Moore, Eduard C. Hurt, Elizabeth Yoder, Howard Sprecher, Arthur A. Spector,
Tópico(s)Adipose Tissue and Metabolism
ResumoThe purpose of this study was to determine whether the formation of docosahexaenoic acid in human cells occurs through a pathway that involves 24carbon n-3 fatty acid intermediates and retroconversion.Normal human skin fibroblasts synthesized radiolabeled docosahexaenoic acid from [ 1-W]18:3n-3, [3-'%]22:5n-3, [3-I4C]24:5n-3, and [3-%]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 a-oxidation or mitochondrial Boxidation, or in normal fibroblasts treated with methyl palmoxirate to inhibit mitochondrial poxidation.Therefore, the retroconversion step in docosahexaenoic acid formation occurs through peroxisomal poxidation.innormal human cells.These results demonstrate that the pathway for docosahexaenoic acid synthesis in human cells involves 24carbon intermediates.The limited ability to synthesize docosahexaenoic acid may underlie some of the pathology that occurs in genetic diseases involving peroxisomal Boxida-
Referência(s)