Competition between 24:5n-3 and ALA for Δ6 desaturase may limit the accumulation of DHA in HepG2 cell membranes

The use of Δ6 desaturase (D6D) twice in the conversion of α-linolenic acid (ALA; 18:3n-3) to docosahexaenoic acid (DHA; 22:6n-3) suggests that this enzyme may play a key regulatory role in the synthesis and accumulation of DHA from ALA. We examined this using an in vitro model of fatty acid metaboli...

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Main Authors: Roxanne Portolesi, Barry C. Powell, Robert A. Gibson
Format: Article
Language:English
Published: Elsevier 2007-07-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S002222752042543X
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author Roxanne Portolesi
Barry C. Powell
Robert A. Gibson
author_facet Roxanne Portolesi
Barry C. Powell
Robert A. Gibson
author_sort Roxanne Portolesi
collection DOAJ
description The use of Δ6 desaturase (D6D) twice in the conversion of α-linolenic acid (ALA; 18:3n-3) to docosahexaenoic acid (DHA; 22:6n-3) suggests that this enzyme may play a key regulatory role in the synthesis and accumulation of DHA from ALA. We examined this using an in vitro model of fatty acid metabolism to measure the accumulation of the long-chain metabolites of ALA in HepG2 cell phospholipids. The accumulation of ALA, eicosapentaenoic acid (20:5n-3), docosapentaenoic acid (22:5n-3), and 24:5n-3 in cell phospholipids was linearly related to the concentration of supplemented ALA over the range tested (1.8–72 μM). The accumulation of the post-D6D products of 22:5n-3, 24:6n-3 and DHA, in cell phospholipids was saturated at concentrations of >18 μM ALA. Supplementation of HepG2 cells with preformed DHA revealed that, although the accumulation of DHA in cell phospholipids approached saturation, the level of DHA in cell phospholipids was significantly greater compared with the accumulation of DHA from ALA, indicating that the accumulation of DHA from ALA was not limited by incorporation. The parallel pattern of accumulation of 24:6n-3 and DHA in response to increasing concentrations of ALA suggests that the competition between 24:5n-3 and ALA for D6D may contribute to the limited accumulation of DHA in cell membranes.
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spelling doaj.art-67ec22957b1841b597aff928a25e03682022-12-21T19:52:40ZengElsevierJournal of Lipid Research0022-22752007-07-0148715921598Competition between 24:5n-3 and ALA for Δ6 desaturase may limit the accumulation of DHA in HepG2 cell membranesRoxanne Portolesi0Barry C. Powell1Robert A. Gibson2Department of Paediatrics and Child Health, Flinders University, Adelaide, AustraliaChild Health Research Institute, North Adelaide, AustraliaNutrition and Functional Food Science, Discipline of Plant and Food Science, School of Agriculture, Food, and Wine, University of Adelaide, Adelaide, AustraliaThe use of Δ6 desaturase (D6D) twice in the conversion of α-linolenic acid (ALA; 18:3n-3) to docosahexaenoic acid (DHA; 22:6n-3) suggests that this enzyme may play a key regulatory role in the synthesis and accumulation of DHA from ALA. We examined this using an in vitro model of fatty acid metabolism to measure the accumulation of the long-chain metabolites of ALA in HepG2 cell phospholipids. The accumulation of ALA, eicosapentaenoic acid (20:5n-3), docosapentaenoic acid (22:5n-3), and 24:5n-3 in cell phospholipids was linearly related to the concentration of supplemented ALA over the range tested (1.8–72 μM). The accumulation of the post-D6D products of 22:5n-3, 24:6n-3 and DHA, in cell phospholipids was saturated at concentrations of >18 μM ALA. Supplementation of HepG2 cells with preformed DHA revealed that, although the accumulation of DHA in cell phospholipids approached saturation, the level of DHA in cell phospholipids was significantly greater compared with the accumulation of DHA from ALA, indicating that the accumulation of DHA from ALA was not limited by incorporation. The parallel pattern of accumulation of 24:6n-3 and DHA in response to increasing concentrations of ALA suggests that the competition between 24:5n-3 and ALA for D6D may contribute to the limited accumulation of DHA in cell membranes.http://www.sciencedirect.com/science/article/pii/S002222752042543Xfatty acid synthesisessential fatty acidsα-linolenic aciddocosahexaenoic acid
spellingShingle Roxanne Portolesi
Barry C. Powell
Robert A. Gibson
Competition between 24:5n-3 and ALA for Δ6 desaturase may limit the accumulation of DHA in HepG2 cell membranes
Journal of Lipid Research
fatty acid synthesis
essential fatty acids
α-linolenic acid
docosahexaenoic acid
title Competition between 24:5n-3 and ALA for Δ6 desaturase may limit the accumulation of DHA in HepG2 cell membranes
title_full Competition between 24:5n-3 and ALA for Δ6 desaturase may limit the accumulation of DHA in HepG2 cell membranes
title_fullStr Competition between 24:5n-3 and ALA for Δ6 desaturase may limit the accumulation of DHA in HepG2 cell membranes
title_full_unstemmed Competition between 24:5n-3 and ALA for Δ6 desaturase may limit the accumulation of DHA in HepG2 cell membranes
title_short Competition between 24:5n-3 and ALA for Δ6 desaturase may limit the accumulation of DHA in HepG2 cell membranes
title_sort competition between 24 5n 3 and ala for δ6 desaturase may limit the accumulation of dha in hepg2 cell membranes
topic fatty acid synthesis
essential fatty acids
α-linolenic acid
docosahexaenoic acid
url http://www.sciencedirect.com/science/article/pii/S002222752042543X
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AT robertagibson competitionbetween245n3andalaford6desaturasemaylimittheaccumulationofdhainhepg2cellmembranes