Chemical modification of microsomal cytochrome P450: role of lysyl residues in hydroxylation activity.
Cytochrome P450 purified from phenobarbital-induced rat liver microsomes was acetylated at 3 lysyl residues. When reconstituted with purified NADPH-cytochrome P450 reductase, the modified cytochrome showed full activity and substrate-induced spectral changes with d-benzphetamine. With 7-ethoxycoumarin, neither enzymic activity nor binding was detected. It is concluded that the positively charged lysine residues of cytochrome P450 are important for metabolism of 7-ethoxycoumarin by cytochrome P450.
D000107:Acetylation; D001665:Binding Sites; D055598:Chemical Phenomena; D002621:Chemistry; D003374:Coumarins / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003640:Dealkylation; D006900:Hydroxylation; D066298:In Vitro Techniques; D008239:Lysine / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism
D003374:Coumarins; C017299:7-ethoxycoumarin; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; D008239:Lysine