Assembling the P450 puzzle: on the sources of nonadditivity in drug metabolism.

ABSTRACT: There is an increasing number of indications of an oversimplification in the premise that the cumulative properties of the human drug-metabolizing ensemble represent a simple aggregate of the properties of the constituting enzymes. Recent studies of the functional effects of hetero-association of multiple cytochrome P450 species and their interactions with metabolically related enzymes revealed a tight integration in the drug-metabolizing ensemble. In our opinion, the sources of interindividual variability in drug metabolism can be elucidated only when considering this ensemble as a multienzyme system, the functional parameters of which are determined by interactions between its constituents. In this article, we present a conceptual model providing a mechanistic explanation for the functio

SUBMITTER: Davydov DR 

PROVIDER: S-EPMC8595691 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature