Regulation of dolichol and of cholesterol biosynthesis in cholesterol-fed rabbits |
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Authors: | David A White Bruce Middleton Sylva Pawson Judith P Bradshaw Richard J Clegg Frank W Hemming GDuncan Bell |
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Institution: | 1. Department of Biochemistry, University of Nottingham, Medical School, Queen''s Medical Center, Nottingham NG7 2UH U.K.;2. Department of Therapeutics, City Hospital, Nottingham NG5 1PD, United Kingdom |
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Abstract: | The feeding of rabbits with a diet supplemented with 2% cholesterol caused a significant increase in the concentration of serum and hepatic microsomal cholesterol while not affecting serum high-density lipoprotein cholesterol concentration. The concentration of cytochrome b5 was also increased in the cholesterol-fed rabbits but no change in the concentration of cytochrome P-450 was apparent. The increase in microsomal cholesterol was accompanied by an inhibition of hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase and a marked stimulation of acyl-coenzyme A:cholesterol acyltransferase activity. The incorporation of 1-14C]acetate into cholesterol and dolichol was strongly inhibited in liver slices of cholesterol-fed animals. In contrast, while incorporation of 2-14C]mevalonate into cholesterol was also inhibited by approximately 90%, incorporation of this precursor into dolichol was stimulated fourfold. The increased incorporation of mevalonate into dolichol was consistent with a threefold increase in the activity of the dolichol phosphate-dependent mannosyl transferase. The possible significance of these differences is discussed. |
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