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.
Highlights
The 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
It is either obtained preformed in the diet or synthesized from n-3 fatty acid precursors such as linolenic acid (18:3) and eicosapentaenoic acid (20:5) [6,7,8]. Synthesis from these precursors involves a series of chain elongation and desaturation reactions [9].The final reaction in this pathway has long been thought to be the conversion of docosapentaenoic acid (22:5n-3) to docosahexaenoic acid FBS (DHA) mediated by an acyECoA 4desaturase
As the direct studies of this new pathway have been restricted to rat liver and indirect supportive evidence limited to studies in the cat [12], the present study was designed to determine whether 24:5 and 24:6 are intermediates in DHA synthesis in intact human cells and, if so, to further determine how 246 is converted to DHA
Summary
The 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. Human skin fibroblastswere chosen for this work because mutant cell lines deficient in peroxisomal and Docosahexaenoic acid (DHA or 22:6), the most abundant n-3 fatty acid normally present in human and animal tissues, has important effects on membrane structure and function[1,2].Phospholipidsthat contain DHA form structural domains in the lipid bilayer that are optimal for the function of certain integral proteins involved in signal transduction or membrane transport [3,4,5].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
