Kuroda M, Endo A
Biochim Biophys Acta. 1976 Jan 18;486(1):70-81.
Inhibitory effect of 44 species of fatty acids on cholesterol synthesis has been examined with a rat liver enzyme system. In the case of saturated fatty acids, the inhibitory activity increased with chain length to a maximum at 11 to 14 carbons, after which activity decreased rapidly. The inhibition increased with the degree of unsaturation of fatty acids. Introduction of a hydroxy group at the alpha-position of fatty acids abolished the inhibition, while the inhibition was enhanced by the presence of a hydroxy group located in an intermediate position of the chain. Branched chain fatty acids having a methyl group at the terminal showed much higher activity than the corresponding saturated straight chain fatty acids with the same number of carbons. With respect to the mechanism for inhibition, tridecanoate was found to inhibit acetoacetyl-CoA thiolase specifically without affecting the other reaction steps in the cholesterol synthetic pathway. The highly unsaturated fatty acids, arachidonate and linoleate, were specific inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA synthase. On the other hand, ricinoleate (hydroxy acid) and phytanate (branched-chain acid) diminished the conversion of mevalonate to sterols by inhibiting a step or steps between squalene and lanosterol.
利用大鼠肝脏酶系统检测了44种脂肪酸对胆固醇合成的抑制作用。就饱和脂肪酸而言，其抑制活性随碳链长度增加而增强，在碳链长度为11至14个碳时达到最大值，之后活性迅速下降。脂肪酸的抑制作用随不饱和度的增加而增强。在脂肪酸的α位引入羟基会消除抑制作用，而位于碳链中间位置的羟基则会增强抑制作用。末端带有甲基的支链脂肪酸比具有相同碳原子数的相应饱和直链脂肪酸表现出更高的活性。关于抑制机制，发现十三烷酸能特异性抑制乙酰乙酰辅酶A硫解酶，而不影响胆固醇合成途径中的其他反应步骤。高度不饱和脂肪酸花生四烯酸和亚油酸是3-羟基-3-甲基戊二酰辅酶A合酶的特异性抑制剂。另一方面，蓖麻油酸（羟基酸）和植烷酸（支链酸）通过抑制角鲨烯和羊毛甾醇之间的一个或多个步骤，减少了甲羟戊酸向甾醇的转化。
