Cooperativity in oxidations catalyzed by cytochrome P450 3A4

Biochemistry
Y F UengF P Guengerich

Abstract

Cytochrome P450 (P450) 3A4 is the most abundant human P450 and oxidizes a diversity of substrates, including various drugs, steroids, carcinogens, and macrolide natural products. In some reactions, positive cooperativity has been reported in microsomal studies. Flavonoids, e.g., 7,8-benzoflavone (alpha-naphthoflavone, alpha NF), have been shown to stimulate some reactions but not others. In systems containing purified recombinant bacterial P450 3A4, positive cooperativity was seen in oxidations of several substrates, including testosterone, 17 beta-estradiol, amitriptyline, and most notably aflatoxin (AF) B1. With these and other reactions, alpha NF typically reduced cooperativity (i.e., the n value in a Hill plot) while either stimulating or inhibiting reactions. With the substrate AFB1, alpha NF both stimulated 8,9-epoxidation and inhibited 3 alpha-hydroxylation. The same patterns were seen with AFB1 in a fused P450 3A4-NADPH-P450 reductase protein. alpha NF did not alter patterns of activity plotted as a function of NADPH-P450 reductase concentration in systems containing the individual proteins. The patterns of AFB1 oxidation to the two products were modified considerably in systems in which NADPH-P450 reductase was replace...Continue Reading

References

Jan 1, 1992·Critical Reviews in Toxicology·S A Wrighton, J C Stevens
Jun 1, 1991·Journal of Medicinal Chemistry·F P GuengerichP Berntsson
Aug 1, 1994·British Journal of Clinical Pharmacology·T AnderssonD J Birkett
May 1, 1965·Journal of Molecular Biology·J MONODJ P CHANGEUX

❮ Previous
Next ❯

Citations

Jan 8, 2004·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Toshiyuki OkutomiSumio Hoka
Jul 16, 2008·Analytical and Bioanalytical Chemistry·Emre M Isin, F Peter Guengerich
Dec 5, 2002·Archives of Biochemistry and Biophysics·F Peter Guengerich
Jan 23, 2002·Chemico-biological Interactions·Petr HodekMarie Stiborová
Jul 24, 1998·Mutation Research·F P GuengerichS Langouët
Nov 27, 1999·Molecular Aspects of Medicine·J A Hasler
Nov 28, 2002·Pharmacology & Therapeutics·Bent H Havsteen
Jan 11, 2001·Biochimica Et Biophysica Acta·C S MilesS K Chapman
Oct 31, 2002·Advanced Drug Delivery Reviews·Jatinder K LambaKenneth E Thummel
Sep 9, 1999·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·D E GoegerK E Anderson
Mar 30, 2002·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Larry C Wienkers
Jun 9, 2001·Mutation Research·F P Guengerich
Nov 19, 2013·Inorganic Chemistry·Nikhil TaxakPrasad V Bharatam
Aug 8, 2009·Nature Protocols·Christal D SohlF Peter Guengerich
Oct 15, 2005·Nature Reviews. Drug Discovery·Larry C Wienkers, Timothy G Heath
Sep 18, 2001·European Journal of Biochemistry·P Hlavica, D F Lewis
Oct 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·A R DunnB R Crane
Jun 17, 1998·Proceedings of the National Academy of Sciences of the United States of America·G R Harlow, J R Halpert
Apr 8, 2011·The Journal of Biological Chemistry·Raku Shinkyo, F Peter Guengerich
Dec 14, 2011·The Journal of Biological Chemistry·Irina F Sevrioukova, Thomas L Poulos
Dec 24, 2011·The Journal of Biological Chemistry·Dmitri R DavydovJames R Halpert
Jun 25, 2002·Journal of Toxicology and Environmental Health. Part a·Terry R Van VleetRoger A Coulombe
Mar 3, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Katerina LevováMarie Stiborová
Jun 30, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Mingyan ZhouJoanne Wang
Aug 22, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Michael Zhuo WangMary F Paine
Dec 22, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ping KangMaria Almira Correia
Feb 2, 2002·Applied and Environmental Microbiology·Bruno BühlerAndreas Schmid
Aug 5, 2003·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Xu Lu, Jeffrey C Hansen
May 23, 1998·Annual Review of Pharmacology and Toxicology·K E Thummel, G R Wilkinson

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.