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.