An alternate pathway to long-chain polyunsaturates: the FADS2 gene product Δ8-desaturates 20:2n-6 and 20:3n-3
An alternate pathway to long-chain polyunsaturates: the FADS2 gene product Δ8-desaturates 20:2n-6 and 20:3n-3
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DOI：
10.1194/jlr.m800630-jlr200
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发表时间：
2009-06-01
影响因子：
6.5
通讯作者：
Brenna, J. Thomas
中科院分区：
文献类型：
--
作者：
Park, Woo Jung;Kothapalli, Kumar S. D.;Brenna, J. Thomas
哺乳动物中由脂肪酸去饱和酶2(FADS2；HSA11q12-q13.1)编码的Delta 6-去饱和酶(FADS2；HSA11q12-q13.1)催化长链多不饱和脂肪酸生物合成的第一步，也是限速步骤。已知FADS2至少作用于五种底物，我们假设FADS2基因产物具有Delta 8-去饱和酶活性。将其转化到酿酒酵母中，可以脱除11，14-二十碳二烯酸(20：2N-6)和11，14，17-二十碳三烯酸(20：3N-3)，分别得到20：3N-6和20：4N-3。竞争实验表明，Delta 8-去饱和度比20：2N-6多3倍的活性。相似的实验表明，对于n-6(18：2n-6 vs 20：2n-6)和n-3(18：3n-3 vs 20：3n-3)，Delta 6-去饱和酶活性分别是Delta 8-去饱和酶活性的7倍和23倍。在哺乳动物中，20：3n-6是前列腺素E1和血栓素B1的直接前体。20：3n-6和20：4n-3也分别是长链多不饱和脂肪酸花生四烯酸和二十碳五烯酸的直接前体。这些发现为哺乳动物长链多不饱和脂肪酸的一种新的生物合成路线提供了明确的分子证据。--Park、W.J.、K.S.D.Kothapalli、P.Lawrence、C.Tyburczy和J.T.Brenna。通向长链多不饱和的另一条途径：FADS2基因产物Delta 8-去饱和20：2n-6和20：3n-3。J.Lipid Res.2009年。50：1195-1202。
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.