INHIBITION OF INVITRO CHOLESTEROL-SYNTHESIS BY FATTY-ACIDS

  • 1 January 1977
    • journal article
    • research article
    • Vol. 486  (1) , 70-81
Abstract
Inhibitory effect of 44 spp. of fatty acids on cholesterol synthesis was 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 11-14 carbons, after which activity decreased rapidly. The inhibition increased with the degree of unsaturation of fatty acids. Introduction of an OH group at the .alpha.-position of fatty acids abolished the inhibition, while the inhibition was enhanced by the presence of an OH group located in an intermediate position of the chain. Branched chain fatty acids having a CH group at the terminal showed much higher activity than the corresponding saturated, straight chain fatty acids with the same number of C. With respect to the mechanism for inhibition, tridecanoate inhibited 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. 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.