Abstract
The use of Delta 6 desaturase (D6D) twice in the conversion of alpha-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 microM). 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 microM 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.
Highlights
The use of #6 desaturase (D6D) twice in the conversion of a-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
The synthesis of long-chain polyunsaturated fatty acids (LCPUFAs) from a-linolenic acid (ALA; 18:3n-3) and linoleic acid (LA; 18:2n-6) is well documented, yet regulation of the pathway, the regulation of the conversion of ALA to docosahexaenoic acid (DHA; 22:6n-3), remains a focus of investigation. This is attributable to the observation that increased dietary intakes of ALA in animals and humans result in an increased level of eicosapentaenoic acid (EPA; 20:5n-3) but little or no change in the level of DHA in tissues or plasma [1,2,3]
The level of EPA in HepG2 cell phospholipids increased by 47-fold, from 0.15 6 0.02% total fatty acids in unsupplemented cells to 7.07 6 0.74% total fatty acids in cells supplemented with 72 mM ALA
Summary
The use of #6 desaturase (D6D) twice in the conversion of a-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. Ingested ALA has several metabolic fates, including b-oxidation, carbon recycling, conversion to LCPUFA, and direct incorporation into structural lipids [7] The balance between these metabolic fates influences the accumulation of DHA from ALA in tissues. We examined the accumulation of DHA in HepG2 cell membranes when supplied preformed in the cell culture medium
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