Hepatic 3-hydroxy-3-methylglutaryl coenzyme-a reductase of rats fed semipurified and stock diets.

Rat hepatic 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMG-CoA reductase) was found to be lower in rats fed a semipurified diet of sucrose, casein, and cellulose with a mixture of safflower oil and stripped lard than those fed a stock diet: 0.115 versus 0.447 nmoles mevalonic acid formed/minute/mg microsomal protein. Efforts were made to find the substances in the stock diet responsible for the higher enzyme activity. Neither the addition of small amounts of cholesterol or plant sterols to the semipurified diet, nor the substitution of corn oil or the lipids extracted from the stock diet for the safflower oil-stipped lard mixture, significantly raised the enzyme level. Replacement of sucrose by starch also had no effect on the enzyme activity. The substitution of soybean protein for the casein did increase the specific activity of the enzyme from 0.115 to 0.247, still well below the 0.447 level response to stock rat diet ingestion. Substitution of the safflower oil-stripped lard fat mixture for the extracted fat of the stock feed had no significant effect on the response of the rats to the stock feed. However, substitution of part of the cellulose in the semi-purified diet with citrus pectin resulted in HMG-CoA levels of 0.553, approximately equal to that produced by the stock diet. In the latter study, the total fecal bile acids of the rat fed the stock, semipurified-cellulose, and semipurified-pectin diets were 2.34, 1.28, and 2.22 mg/g feces respectively, and the total fecal neutral sterols 1.86, 1.50, and 2.42 mg/g feces. Thus, the constituent nonutritive fiber appears responsible for differences in steroid excretion and elevated hepatic HMG-CoA levels, possibly by binding bile acids and increasing the turnover rate of blood and liver cholesterol.