REGULATION OF ACYL COA-CHOLESTEROL ACYLTRANSFERASE BY 25-HYDROXYCHOLESTEROL IN RABBIT INTESTINAL MICROSOMES AND ABSORPTIVE CELLS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 24  (8) , 1049-1059
Abstract
The regulation of rabbit intestinal acyl CoA:cholesterol acyltransferase (ACAT) by 25-hydroxycholesterol was studied. 25-Hydroxycholesterol significantly increased jejunal microsomal ACAT activity. The stimulation of ACAT activity by 25-hydroxycholesterol was inversely related to microsomal cholesterol content. In enterocytes, 25-hydroxycholesterol stimulated cholesteryl ester synthesis 6-fold. The esterification of cholesterol, taken up by enterocytes from liposomes or bile salt micelles, was increased by 25-hydroxycholesterol. This, however, did not affect the rate of uptake of cholesterol by the cells. In intestinal cells from rabbits fed cholesterol, the effect of 25-hydroxycholesterol on cholesteryl ester synthesis was 50% of that in cells prepared from animals fed no cholesterol. 25-Hydroxycholesterol stimulated the esterification of newly synthesized cholesterol. As new free cholesterol increased in enterocytes, 25-hydroxycholesterol lost its effect. Despite large amounts of newly synthesized cholesterol, oleic acid incorporation into cholesteryl ester was not increased. 25-Hydroxycholesterol apparently increases intestinal ACAT activity. The effect of 25-hydroxycholesterol on ACAT is dependent upon the availability of cholesterol to the enzyme. At cholesterol concentrations below saturation, the oxygenated sterol has a stimulatory effect. If ACAT is saturated, 25-hydroxycholesterol has no effect. ACAT catalyzes the esterification of 2 separate pools of cholesterol within the enterocyte, i.e., newly synthesized cholesterol and membrane cholesterol. 25-Hydroxycholesterol increases the esterification rate of cholesterol in both pools.

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