Twenty years of biochemistry of human P450s - Purification, expression, mechanism, and relevance to drugs

Today cytochrome P450 (P450) research is accepted as an integral part of dr ug development and discovery. Work leading to this point included biochemic al studies on P450 in experimental animal models and application to human s ystems. The development of recombinant expression systems has been an impor tant part of the progress, and in this article we describe some recently de veloped bacterial systems that can be used for the production of metabolite s, genotoxicity testing, and screening in random mutagenesis work. Rate-lim iting aspects of P450 reactions vary with particular systems, and further i nvestigations are in order. Non-ionic detergents have been utilized widely in P450 purification work; these compounds are now shown to be substrates f or P450s. These oxidations are not only of fundamental interest in expandin g the repertoire of P450 substrates but have significance in light of human exposure to these compounds.