Murray J D, Oberbauer A M, Sharp K R, German J B
Department of Animal Science, School of Veterinary Medicine, University of California, Davis 95616.
Transgenic Res. 1994 Jul;3(4):241-8. doi: 10.1007/BF02336777.
The degree of unsaturation of membrane lipids has been implicated in a number of physiological disorders, yet its regulation remains poorly understood, especially the regulation of the synthesis and distribution of arachidonic acid levels, the most abundant long chain polyunsaturated fatty acid in membranes. Transgenic mice expressing the ovine metallothionein 1a-ovine growth hormone (oMt1a-oGH) fusion gene exhibited significantly elevated levels of a number of long chain polyunsaturated fatty acids in serum, including arachidonic acid. In oMt1a-oGH transgenic mice the products of all three desaturation pathways are affected by the expression of the ovine growth hormone transgene. The essential precursors of membrane long chain polyunsaturated fatty acids, 18:2n-6 and 18:3n-3, were reduced in transgenics relative to controls, and their desaturation and elongation products, arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3), were elevated. As rare intermediate long chain polyunsaturated fatty acids such as eicosatrienoic acid (20:3n-9) were also significantly elevated, we conclude that these observations reflect increased activity of the delta-5 and delta-6 desaturase enzymes. In contrast, the products of the stearoyl CoA or delta-9 desaturase, were significantly reduced in oMt1a-oGH expressing transgenics relative to their levels in control mice.
膜脂的不饱和度与多种生理紊乱有关，但其调节机制仍知之甚少，尤其是花生四烯酸水平的合成和分布调节，花生四烯酸是膜中最丰富的长链多不饱和脂肪酸。表达绵羊金属硫蛋白1a-绵羊生长激素（oMt1a-oGH）融合基因的转基因小鼠血清中多种长链多不饱和脂肪酸水平显著升高，包括花生四烯酸。在oMt1a-oGH转基因小鼠中，所有三种去饱和途径的产物都受到绵羊生长激素转基因表达的影响。相对于对照组，转基因小鼠中膜长链多不饱和脂肪酸的必需前体18:2n-6和18:3n-3减少，而它们的去饱和和延长产物花生四烯酸（20:4n-6）和二十二碳六烯酸（22:6n-3）升高。由于稀有中间长链多不饱和脂肪酸如二十碳三烯酸（20:3n-9）也显著升高，我们得出结论，这些观察结果反映了δ-5和δ-6去饱和酶活性的增加。相反，相对于对照小鼠，表达oMt1a-oGH的转基因小鼠中硬脂酰辅酶A或δ-9去饱和酶的产物显著减少。
