Rate-Limiting Steps in Cytochrome P450 Catalysis
-
F. P. Guengerich
Abstract
Cytochrome P450 (P450) reactions are of interest because of their relevance to the oxidative metabolism of drugs, steroids, carcinogens, and other chemicals. One of the considerations about functional characterization is which steps of the catalytic cycle are ratelimiting. Detailed analysis indicates that several different steps can be ratelimiting with individual P450 reactions. NDealkylation of parasubstituted N,Ndimethylanilines is a function of the electron withdrawing/donating properties of the substituent and the oxidationreduction potential of the substrate, supporting a role in ratelimiting electron transfer from substrate to the high valent P450. In the oxidations of ethanol and acetaldehyde by human P450 2E1, a step following product formation must be the slow step (but not product release per se). Several oxidations catalyzed by human P450s 1A2 and 2D6 show slow CH bond breaking, and apparent highvalent iron complexes accumulate in the reaction steadystate. Kinetic simulations were used to test the suitability of potential schemes and to probe the effects of changes in individual reaction steps.
Copyright © 2002 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- Biological Chemistry 125th Anniversary
- Kai Simons Felix Hoppe-Seyler Lecturer 2002
- Lipid Rafts in Protein Sorting and Cell Polarity in Budding Yeast Saccharomyces cerevisiae
- Paper of the Year 2001
- RNA-Mediated RNA Degradation in Transgene- and Virus-Induced Gene Silencing
- Immunopharmacology of CpG DNA
- Induction and Regulation of Endogenous Granulocyte Colony-Stimulating Factor Formation
- In the Cellular Garden of Forking Paths: How p38 MAPKs Signal for Downstream Assistance
- The Human Steroid Hydroxylases CYP11B1 and CYP11B2
- Rate-Limiting Steps in Cytochrome P450 Catalysis
- YidC, a Newly Defined Evolutionarily Conserved Protein, Mediates Membrane Protein Assembly in Bacteria
- Vascular Endothelial Growth Factor Receptor Family Genes: When Did the Three Genes Phylogenetically Segregate?
- The TNFTNF Receptor System
- Fast Regulation of Cytochrome P450 Activities by Phosphorylation and Consequences for Drug Metabolism and Toxicity
- Protein Transduction: A Novel Tool for Tissue Regeneration
- NF-κB A Potential Therapeutic Target for Inhibition of Human Cytomegalovirus (Re)activation?
- Three-State Equilibrium of Escherichia coli Trigger Factor
- Binding of a C-Terminal Fragment (Residues 369 to 435) of Vitamin D-Binding Protein to Actin
- The Hyaluronan-Binding Serine Protease from Human Plasma Cleaves HMW and LMW Kininogen and Releases Bradykinin
- Jasmonate-Induced Lipid Peroxidation in Barley Leaves Initiated by Distinct 13-LOX Forms of Chloroplasts
- Real-Time Determination of Telomerase Activity in Cell Extracts Using an Optical Biosensor
- Study of Chaperone-Like Activity of Human Haptoglobin: Conformational Changes under Heat Shock Conditions and Localization of Interaction Sites
Articles in the same Issue
- Biological Chemistry 125th Anniversary
- Kai Simons Felix Hoppe-Seyler Lecturer 2002
- Lipid Rafts in Protein Sorting and Cell Polarity in Budding Yeast Saccharomyces cerevisiae
- Paper of the Year 2001
- RNA-Mediated RNA Degradation in Transgene- and Virus-Induced Gene Silencing
- Immunopharmacology of CpG DNA
- Induction and Regulation of Endogenous Granulocyte Colony-Stimulating Factor Formation
- In the Cellular Garden of Forking Paths: How p38 MAPKs Signal for Downstream Assistance
- The Human Steroid Hydroxylases CYP11B1 and CYP11B2
- Rate-Limiting Steps in Cytochrome P450 Catalysis
- YidC, a Newly Defined Evolutionarily Conserved Protein, Mediates Membrane Protein Assembly in Bacteria
- Vascular Endothelial Growth Factor Receptor Family Genes: When Did the Three Genes Phylogenetically Segregate?
- The TNFTNF Receptor System
- Fast Regulation of Cytochrome P450 Activities by Phosphorylation and Consequences for Drug Metabolism and Toxicity
- Protein Transduction: A Novel Tool for Tissue Regeneration
- NF-κB A Potential Therapeutic Target for Inhibition of Human Cytomegalovirus (Re)activation?
- Three-State Equilibrium of Escherichia coli Trigger Factor
- Binding of a C-Terminal Fragment (Residues 369 to 435) of Vitamin D-Binding Protein to Actin
- The Hyaluronan-Binding Serine Protease from Human Plasma Cleaves HMW and LMW Kininogen and Releases Bradykinin
- Jasmonate-Induced Lipid Peroxidation in Barley Leaves Initiated by Distinct 13-LOX Forms of Chloroplasts
- Real-Time Determination of Telomerase Activity in Cell Extracts Using an Optical Biosensor
- Study of Chaperone-Like Activity of Human Haptoglobin: Conformational Changes under Heat Shock Conditions and Localization of Interaction Sites
