Mechanism-based inactivation of cytochromes P450 2E1 and 2B1 by 5-phenyl-1-pentyne

Archives of Biochemistry and Biophysics
E S RobertsP F Hollenberg

Abstract

A series of acetylenic compounds whose structures were based on "P450 2E1-like" substrates was investigated for their ability to cause inactivation of P450 2E1-dependent p-nitrophenol hydroxylation. The most effective compound with liver microsomes from pyridine-treated rats or with rabbit P450 2E1 in a reconstituted system was 5-phenyl-1-pentyne. The inactivation of purified 2B1, 2E1, a truncated 2E1 lacking amino acids 3-29, 2E1(Delta3-29), or a truncated 2E1 in which threonine 303 was replaced with alanine, 2E1(Delta3-29, T303A), in a reconstituted system by 5-phenyl-1-pentyne was NADPH- and time-dependent and followed pseudo-first-order kinetics. The maximal rate constants for inactivation, the concentrations that gave half-maximal inactivation (KI), and the partition ratios (the number of 5-phenylvaleric acid molecules formed/inactivation event) were determined with each P450. The KI values for 2B1 and 2E1(Delta3-29, T303A) were twice those for 2E1 and 2E1(Delta3-29), and the partition ratios for 2B1 and 2E1(Delta3-29, T303A) were 5-10 times greater than those of 2E1 or 2E1(Delta3-29). During the incubation of P450 2E1 with 5-phenyl-1-pentyne, the loss of P450 as determined by the reduced-CO difference spectra was equal to...Continue Reading

References

Aug 18, 1992·Biochemical Pharmacology·N E HopkinsW L Alworth
Jan 6, 1992·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·D R Koop
Nov 1, 1991·Chemical Research in Toxicology·J F BradyC S Yang
Jul 1, 1990·Chemical Research in Toxicology·D R Koop
Mar 1, 1990·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·H IshizakiC S Yang
Dec 8, 1981·Biochemistry·P R Ortiz de Montellano, K L Kunze
Nov 10, 1995·Archives of Biochemistry and Biophysics·E S RobertsP F Hollenberg
Jul 15, 1996·Archives of Biochemistry and Biophysics·E S RobertsP F Hollenberg

❮ Previous
Next ❯

Citations

May 15, 2003·Journal of Toxicology and Environmental Health. Part a·Gary Carlson
Aug 4, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·John B Morris, Alan R Buckpitt
Aug 21, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Shuijie ShenJiang Zheng
Apr 20, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·James R Halpert
Mar 5, 2010·The Journal of Pharmacology and Experimental Therapeutics·Hsia-lien LinPaul F Hollenberg
Jul 24, 2015·Critical Reviews in Toxicology·Lisa A BaileyLorenz R Rhomberg
Aug 1, 2006·Biochemical and Biophysical Research Communications·Mary Beth GenterDaniel W Nebert
Nov 18, 2000·Journal of Biochemical and Molecular Toxicology·M W Powley, G P Carlson
Mar 22, 2002·The Journal of Pharmacology and Experimental Therapeutics·Hsia-lien LinPaul F Hollenberg
May 5, 2004·The Journal of Pharmacology and Experimental Therapeutics·Andrea C SimmondsPoh-Gek Forkert
Aug 11, 2004·The Journal of Pharmacology and Experimental Therapeutics·Hsia-Lien LinPaul F Hollenberg
Mar 20, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Shigeyuki KitamuraShigeru Ohta
Apr 16, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Stephanie L BornMichael P Purdon
Jun 9, 2005·Toxicology and Industrial Health·James E DennisonMelvin E Andersen
Jun 18, 2019·Drug Metabolism Reviews·Paul R Ortiz de Montellano
Jan 8, 1999·Biochemical and Biophysical Research Communications·S Hu, L P Hager
Jan 16, 2007·Archives of Biochemistry and Biophysics·Samuel L CollomGrover P Miller

❮ 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.