Abstract
Rats maintained on semisynthetic diets show a low rate of acetate incorporation into cholesterol, when compared with rats fed a commercial diet. Addition of a bile acid sequestering anion exchange resin to the semisynthetic diet causes a several-fold increase of hepatic cholesterol synthetic activity. A diurnal rhythm is demonstrated for the incorporation of acetate-1- 14C (but not of mevalonate) into cholesterol by rat liver slices and liver extracts. Synthesis at midnight is increased by a factor of 3.8 over the synthesis which is measurable during the day. The rhythmic activity changes are due to activity changes of the enzyme system synthesizing mevalonate. These rhythmic changes of activity are assumed to be due to alterations of the level of enzyme protein. Cholic acid, when given with the diet, also acts at this enzymic step as inhibitor of cholesterol biosynthesis and is shown to be much more effective than dietary cholesterol, but the concentration levels of cholic acid in liver do not show alterations which can be correlated with the observed rhythmic activity changes under conditions of normal feeding.
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