6533b7dbfe1ef96bd1271610

RESEARCH PRODUCT

Fast Regulation of Cytochrome P450 Activities by Phosphorylation and Consequences for Drug Metabolism and Toxicity

Barbara Oesch-bartlomowiczFranz Oesch

subject

Drug-Related Side Effects and Adverse ReactionsClinical BiochemistryPharmacologyBiochemistryIsozymeCytochrome P-450 Enzyme SystemCyclic AMPAnimalsHumansDrug InteractionsPhosphorylationEnzyme inducerMolecular BiologyCarcinogenchemistry.chemical_classificationbiologyCytochrome P450Cyclic AMP-Dependent Protein KinasesHormonesIsoenzymesenzymes and coenzymes (carbohydrates)EnzymePharmaceutical PreparationsBiochemistrychemistryCytochrome P-450 CYP2B1ToxicityCarcinogensbiology.proteinPhosphorylationDrug metabolism

description

In contrast to the well-known regulation of cytochrome P450 (CYP) activity by enzyme induction, which represents a process with slow onset and slow offset, more recent studies revealed phosphorylation as a fast (within observation instantaneous) and isoenzyme-selective regulation. The phosphorylated enzyme (investigated isozyme: CYP2B1) was fully inactive. The phosphorylation is mediated by PKA and hence under control of hormones and drugs that alter cellular cAMP levels. The consequences for the metabolic control of toxic species derived from drugs and environmental carcinogens are discussed. This information will help to improve therapy with drugs metabolized by CYPs which are phosphorylated by PKA, especially if these drugs possess a narrow window between required effectiveness and unacceptable toxicity.

yearjournalcountryeditionlanguage
2002-11-28Biological Chemistry
https://doi.org/10.1515/bc.2002.179