The functional effects of physical interactions involving cytochromes P450: putative mechanisms of action and the extent of these effects in biological membranes.
Drug Metab Rev
; 48(3): 453-69, 2016 08.
Article
en En
| MEDLINE
| ID: mdl-27500687
ABSTRACT
Cytochromes P450 represent a family of enzymes, which are responsible for the oxidative metabolism of a wide variety of xenobiotics. Although the mammalian P450s require interactions with their redox partners in order to function, more recently, P450 system proteins have been shown to exist as multi-protein complexes that include the formation of P450â¢P450 complexes. Evidence has shown that the metabolism of some substrates by a given P450 can be influenced by the specific interaction of the enzyme with other forms of P450. Detailed kinetic analysis of these reactions in vitro has shown that the P450-P450 interactions can alter metabolism by changing the ability of a P450 to bind to its cognate redox partner, NADPH-cytochrome P450 reductase; by altering substrate binding to the affected P450; and/or by changing the rate of a catalytic step of the reaction cycle. This review summarizes the known examples of P450-P450 interactions that have been shown in vitro to influence metabolism and categorizes them according to the mechanism(s) causing the effects. P450-P450 interactions have the potential to cause major changes in the metabolism and elimination of drugs in vivo. This review summarizes the evidence that the P450-P450 interactions influence metabolism in biological membranes and discusses the studies, which will provide further insight into the extent of these effects in the future.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Membrana Celular
/
Sistema Enzimático del Citocromo P-450
/
Complejos Multiproteicos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Drug Metab Rev
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos