The role of cytochrome P-450 in cholesterol biogenesis and catabolism.
1. Adjuvant-induced arthritis in rats is accompanied by a loss of activity of the drug-metabolizing enzyme system and a decrease in hepatic cytochrome P-450. 2. Arthritic rats have normal serum and liver cholesterol concentrations. 3. The rate of biogenesis of cholesterol in vivo and in vitro from either [(14)C]acetate or [(14)C]mevalonate in arthritic rats was the same as or greater than that found in control rats. 4. Treatment of rats with carbon disulphide (1ml/kg) resulted in a loss of drug-metabolizing-enzyme activity and increased cholesterol biogenesis. 5. The activity of cholesterol 7alpha-hydroxylase in adjuvant-induced arthritic rats did not differ significantly from that in control rats. 6. Rats fed with cholestyramine had an elevated hepatic cholesterol 7alpha-hydroxylase activity, but neither the concentration of cytochrome P-450 nor the activity of the drug-hydroxylating enzyme, aminopyrine demethylase, was affected. 7. The relationships between drug hydroxylation and cholesterol metabolism are discussed.
D000085:Acetates / Q000378:metabolism; D000632:Aminopyrine; D000818:Animals; D001168:Arthritis / Q000378:metabolism; D002246:Carbon Disulfide / Q000494:pharmacology; D002247:Carbon Isotopes; D002784:Cholesterol / Q000032:analysis / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D002792:Cholestyramine Resin / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006900:Hydroxylation; D066298:In Vitro Techniques; D008099:Liver / Q000032:analysis / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D006899:Mixed Function Oxygenases / Q000032:analysis; D010088:Oxidoreductases / Q000032:analysis; D051381:Rats
D000085:Acetates; D002247:Carbon Isotopes; D000632:Aminopyrine; D002792:Cholestyramine Resin; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D002246:Carbon Disulfide; D008798:Mevalonic Acid