Binding of cholesterol to cytochromes P-450 from rabbit liver microsomes.
The ability of different cytochromes P-450 from rabbit liver microsomes to bind cholesterol and to catalyze 7 alpha-hydroxylation of cholesterol was studied. Cytochromes P-450LM2 and P-450LM3b did not bind cholesterol and were inactive in cholesterol 7 alpha-hydroxylation. Cytochrome P-450LM4 from phenobarbital-treated rabbits as well as cytochromes P-450LM4 I and P-450LM4 II from cholestyramine-treated rabbits were able to bind cholesterol. Only cytochrome P-450LM4 II catalyzed 7 alpha-hydroxylation of cholesterol. Cytochrome P-450LM4 II also bound 5-cholestene-3 beta,-7 alpha-diol and 3 beta-hydroxy-5-cholesten-7-one. These compounds competitively inhibited binding of cholesterol. Cholesterol 7 alpha-hydroxylation was inhibited by its product 5-cholestene-3 beta,7 alpha-diol.
D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology; D011817:Rabbits; D013053:Spectrophotometry
D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D010634:Phenobarbital