Journal
JOURNAL OF LIPID RESEARCH
Volume 50, Issue 6, Pages 1195-1202Publisher
ELSEVIER
DOI: 10.1194/jlr.M800630-JLR200
Keywords
polyunsaturated fatty acid biosynthesis; dihomo-gamma-linolenic acid; eicosanoid precursor biosynthesis
Categories
Funding
- National Institutes of Health [GM071534]
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The mammalian Delta 6-desaturase coded by fatty acid desaturase 2 (FADS2; HSA11q12-q13.1) catalyzes the first and rate-limiting step for the biosynthesis of long-chain polyunsaturated fatty acids. FADS2 is known to act on at least five substrates, and we hypothesized that the FADS2 gene product would have Delta 8-desaturase activity. Saccharomyces cerevisiae transformed with a FADS2 construct from baboon neonate liver cDNA gained the function to desaturate 11,14-eicosadienoic acid (20:2n-6) and 11,14,17-eicosatrienoic acid (20:3n-3) to yield 20:3n-6 and 20:4n-3, respectively. Competition experiments indicate that Delta 8-desaturation favors activity toward 20:3n-3 over 20:2n-6 by 3-fold. Similar experiments show that Delta 6-desaturase activity is favored over Delta 8-desaturase activity by 7-fold and 23-fold for n-6 (18:2n-6 vs 20:2n-6) and n-3 (18:3n-3 vs 20:3n-3), respectively. In mammals, 20:3n-6 is the immediate precursor of prostaglandin E1 and thromboxane B1. 20:3n-6 and 20:4n-3 are also immediate precursors of long-chain polyunsaturated fatty acids arachidonic acid and eicosapentaenoic acid, respectively. These findings provide unequivocal molecular evidence for a novel alternative biosynthetic route to long-chain polyunsaturated fatty acids in mammals from substrates previously considered to be dead-end products.-Park, W. J., K. S. D. Kothapalli, P. Lawrence, C. Tyburczy, and J. T. Brenna. An alternate pathway to long-chain polyunsaturates: the FADS2 gene product Delta 8-desaturates 20:2n-6 and 20:3n-3. J. Lipid Res. 2009. 50:1195-1202.
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