Effect of conjugated linoleic acid on Delta-5 desaturase activity in yeast transformed with fungal Delta-5 desaturase gene

Effect of conjugated linoleic acid on Delta-5 desaturase activity in yeast transformed with fungal Delta-5 desaturase gene
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DOI:
10.1023/b:mcbi.0000044303.55141.8c
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发表时间:
2004-10-01
影响因子:
4.3
通讯作者:
Huang, YS
Huang, YS
中科院分区:
生物学3区
文献类型:
--
作者:
Chuang, LT;Thurmond, JM;Huang, YS

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共轭亚油酸(CLA)是一种来源于亚油酸(LA:Delta9,12-18:2)的位置和几何异构体的混合物,通过细胞培养和动物模型的研究表明,CLA具有多种生物学功能。推测共轭亚油酸的有益作用是通过抑制花生四烯酸(AA;Delta5,8,11,14-20:4)的产生,从而抑制促炎二十烷类化合物的产生。在这项研究中,我们以转化真菌Delta5-去饱和酶基因的面包酵母酿酒酵母为模型,研究共轭亚油酸是否影响Delta5-去饱和酶的活性,Delta5-去饱和酶是将二高-伽马亚麻酸(DGLA;Delta8,11,14-20:3)转化为AA的限速步骤。在添加DGLA和四种不同CLA异构体(c9、t11-、t10、c12-、c9、c11-和t9、t11)的培养基中,检测转化酵母中Delta5-去饱和酶的活性。结果表明,4种异构体均易被酵母菌摄取,均能抑制DGLA向AA的转化。四种异构体的抑制程度因介质中添加的CLA异构体的不同而不同。由于部分CLA异构体可以转化为Delta5-CLA代谢物(Delta5,c9,t11-,Delta5,t10,c12-,Delta5,c9,c11-和Delta5,t9,t11-18:3),推测CLA通过底物竞争抑制DGLA向AA的Delta5-去饱和化。
Conjugated linoleic acid (CLA), a mixture of positional and geometric isomers derived from linoleic acid (LA: Delta9, 12-18:2), has been shown to exhibit various biological functions based on studies using cell culture and animal models. It was postulated that the beneficial effects of CLA were exerted through suppression of production of arachidonic acid (AA; Delta5,8,11,14-20:4) and consequently, production of pro-inflammatory eicosanoids. In this study, we used the baker's yeast, Saccharomyces cerevisiae, transformed with fungal Delta5-desaturase gene as a model, to study whether CLA affects the activity of Delta5-desaturase, a rate-limiting step which converts dihomo-gamma-linolenic acid (DGLA; Delta8,11, 14-20:3) to AA. The activity of Delta5-desaturase was examined in the transformed yeast incubated in a medium supplemented with DGLA and one of four different CLA isomers (c9, t11-, t10, c12-, c9, c11- and t9, t11). Results show that all four isomers were taken up readily by the yeast, and all of them suppressed the conversion of DGLA to AA. The degree of suppression, which varied significantly among four isomers was modulated by the level of CLA isomers added in the medium. Since portions of these CLA isomers could be converted to form Delta5-CLA metabolites (Delta5, c9, t11-, Delta5, t10, c12-, Delta5, c9, c11- and Delta5, t9, t11- 18: 3), it is suggested that CLA suppressed the Delta5-desaturation of DGLA to AA through substrate competition between DGLA and CLA isomers.