Evolution of the cytochrome P450 superfamily: sequence alignments and pharmacogenetics.

摘要: The evolution of the cytochrome P450 (CYP) superfamily is described, with particular reference to major events in development biological forms during geological time. It noted that currently accepted timescale for elaboration phylogenetic tree exhibits close parallels terrestrial biota. Indeed, present human complement xenobiotic-metabolizing enzymes may have originated from coevolutionary 'warfare' between plants and animals Devonian period about 400 million years ago. A number key correspondences system course over time, point a mechanistic molecular biology which consistent steady increase atmospheric oxygenation beginning 2000 ago, whereas dietary changes more recent time provide one possible explanation certain species differences metabolism. Alignment protein sequences within same family or subfamily, together across-family comparisons, aid rationalization drug metabolism specificities different isoforms, can assist an understanding genetic polymorphisms P450-mediated oxidations at level. Moreover, variation regulatory mechanisms inducibilities mammalian are likely important implications current procedures chemical safety evaluation, rely on pure strains laboratory bred rodents testing compounds destined exposure.