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Metabolic fate of docosahexaenoic acid ( DHA ; 22:6n‐3) in human cells: direct retroconversion of DHA to eicosapentaenoic acid (20:5n‐3) dominates over elongation to tetracosahexaenoic acid (24:6n‐3)
Author(s) -
Park Hui Gyu,
Lawrence Peter,
Engel Matthew G.,
Kothapalli Kumar,
Brenna James Thomas
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12368
Subject(s) - docosahexaenoic acid , eicosapentaenoic acid , docosapentaenoic acid , biochemistry , enzyme , biology , fatty acid , chemistry , polyunsaturated fatty acid
Docosahexaenoic acid (22:6n‐3) supplementation in humans causes eicosapentaenoic acid (20:5n‐3) levels to rise in plasma, but not in neural tissue where 22:6n‐3 is the major omega‐3 in phospholipids. We determined whether neuronal cells (Y79 and SK ‐N‐ SH ) metabolize 22:6n‐3 differently from non‐neuronal cells ( MCF 7 and HepG2). We observed that 13 C‐labeled 22:6n‐3 was primarily esterified into cell lipids. We also observed that retroconversion of 22:6n‐3 to 20:5n‐3 was 5‐ to 6‐fold greater in non‐neural compared to neural cells and that retroconversion predominated over elongation to tetracosahexaenoic acid (24:6n‐3) by 2–5‐fold. The putative metabolic intermediates, 13 C‐labeled 22:5n‐3 and 13 C‐labeled 24:5n‐3, were not detected in our assays. Analysis of the expression of enzymes involved in fatty acid beta‐oxidation revealed that MCF 7 cells abundantly expressed the mitochondrial enzymes CPT 1A, ECI 1, and DECR 1, whereas the peroxisomal enzyme ACOX 1 was abundant in HepG2 cells, thus suggesting that the initial site of 22:6n‐3 oxidation depends on the cell type. Our data reveal that non‐neural cells more actively metabolize 22:6n‐3 to 20:5n‐3 via channeled retroconversion, while neural cells retain 22:6n‐3.