On the general mechanism of selective induction of cytochrome P450 enzymes by chemicals: some theoretical considerations.
BACKGROUND
The CYP isoforms that are selectively induced following exposure to structurally-diverse chemicals often are the ones capable of metabolizing these chemicals. However, the molecular mechanism underlying this apparent functional coupling is not understood at present.


METHODS
Three hypotheses are developed to explain the complex process of selective chemical induction of CYPs: i) each inducible CYP may have a corresponding intracellular receptor that interacts with the inducer chemical and mediates the selective induction of this CYP; ii) each inducible CYP and its corresponding receptor may share highly similar steric structures for their substrate/inducer-binding sites and iii) each chemically-inducible CYP gene may have distinct genomic response element(s) that interact selectively with the corresponding receptor.


RESULTS
The readers are introduced to a novel theoretical framework that offers a plausible mechanistic explanation at the molecular level concerning the complex process of how an organism selectively activates the biosynthesis of certain CYP isoform(s) that can effectively metabolize a chemical to which the organism is exposed.


CONCLUSIONS
The theoretical framework developed herein seeks to ignite additional critical thinking on this important research subject as well as to promote experimental testing of the proposed theories in the future. Undoubtedly, these studies will enhance the understanding of the molecular mechanisms for the selective induction of CYP enzymes by chemicals.
Zhu
Bao Ting
BT
University of Kansas Medical Center, Department of Pharmacology, Toxicology and Therapeutics, MS-1018, Room KLSIC-4061, 2146 W. 39th Ave, Kansas City, KS 66160, USA. BTZhu@kumc.edu
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000502:physiology*; D004790:Enzyme Induction / Q000502:physiology*; D006801:Humans; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000502:physiology
D018160:Receptors, Cytoplasmic and Nuclear; D003577:Cytochrome P-450 Enzyme System