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Journal of Lipid Research, Vol. 48, 1592-1598, July 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Competition between 24:5n-3 and ALA for 6 desaturase may limit the accumulation of DHA in HepG2 cell membranes

Roxanne Portolesi^*, Barry C. Powell and Robert A. Gibson^1,

^* Department of Paediatrics and Child Health, Flinders University, Adelaide, Australia
Child Health Research Institute, North Adelaide, Australia
Nutrition and Functional Food Science, Discipline of Plant and Food Science, School of Agriculture, Food, and Wine, University of Adelaide, Adelaide, Australia

Published, JLR Papers in Press, April 4, 2007.

¹ To whom correspondence should be addressed. e-mail: robert.gibson{at}adelaide.edu.au

The use of 6 desaturase (D6D) twice in the conversion of -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.

Supplementary key words fatty acid synthesis • essential fatty acids • -linolenic acid • docosahexaenoic acid

Abbreviations: ALA, -linolenic acid; D6D, 6 desaturase; DHA, docosahexaenoic acid; DPA, docosapentaenoic acid; EPA, eicosapentaenoic acid; FAME, fatty acid methyl ester; LA, linoleic acid; LCPUFA, long-chain polyunsaturated fatty acid

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