Human carbonyl reduction pathways and a strategy for their study in vitro

Drug Metabolism Reviews
M Jane Cox Rosemond, John S Walsh

Abstract

Carbonyl reduction plays a significant role in physiological processes throughout the body. Although much is known about endogenous carbonyl metabolism, much less is known about the roles of carbonyl-reducing enzymes in xenobiotic metabolism. Multiple pathways exist in humans for metabolizing carbonyl moieties of xenobiotics to their corresponding alcohols, readying these molecules for subsequent conjugation and/or excretion. When exploring carbonyl reduction clearance pathways for a drug development candidate, it is possible to assess the relative contributions of these enzymes due to their differences in subcellular locations, cofactor dependence, and inhibitor profiles. In addition, the contributions of these enzymes may be explored by varying incubation conditions, such as pH. Presently, individual isoforms of carbonyl-reducing enzymes are not widely available, either in recombinant or purified form. However, it is possible to study carbonyl reduction clearance pathways from simple experiments with commercially available reagents. This article provides an overview of carbonyl-reducing enzymes, including some kinetic data for substrates and inhibitors. In addition, an experimental strategy for the study of these enzymes in v...Continue Reading

References

Jan 1, 1978·Biochemical Pharmacology·N K AhmedN R Bachur
Dec 1, 1992·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·H Wirth, B Wermuth
Sep 1, 1992·Biochemical Pharmacology·D W Eyles, S M Pond
Dec 11, 1991·Biochemical Pharmacology·E MaserK J Netter
Apr 1, 1991·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·M Strolin BenedettiP Dostert
Apr 1, 1991·Clinical Pharmacokinetics·B PerssonT Hedner
Jan 1, 1990·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·W R RushD J Graham
Jan 1, 1989·Cardiology·J Caldwell
Jan 1, 1988·Journal of Medicinal Chemistry·R SargesM J Peterson
Oct 1, 1987·Journal of Clinical Psychopharmacology·K K MidhaG McKay
Jan 1, 1985·Biochemical Pharmacology·T NakayamaH Sawada
Nov 1, 1984·Steroids·C Monder, C H Shackleton
Sep 1, 1983·Journal of Medicinal Chemistry·M Rossi
Jan 1, 1980·Drug Metabolism Reviews·R L Felsted, N R Bachur
Apr 1, 1994·The Histochemical Journal·K MatsuuraH Sawada
Nov 1, 1993·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·R R Shah
Apr 22, 1993·Biochemical Pharmacology·N IwataT Satoh
Feb 1, 1993·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·M Strolin BenedettiL Gianni
Dec 1, 1995·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·U Breyer-Pfaff, K Nill
May 1, 1996·Clinical Endocrinology·P M Stewart
Dec 1, 1996·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·E A RekkaE Maser

❮ Previous
Next ❯

Citations

Mar 9, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Vanessa Gonzalez-CovarrubiasJavier G Blanco
Nov 22, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Vanessa Gonzalez-CovarrubiasJavier G Blanco
Sep 15, 2006·Annual Review of Pharmacology and Toxicology·Yi Jin, Trevor M Penning
Nov 1, 2013·Drug Metabolism Reviews·Petra Malátková, Vladimír Wsól
Mar 22, 2007·Journal of Enzyme Inhibition and Medicinal Chemistry·Yorishige ImamuraHideaki Shimada
Oct 25, 2008·Drug Metabolism Reviews·Oleg A BarskiAruni Bhatnagar
Jan 30, 2010·Biochemical Pharmacology·Chunze LiThomayant Prueksaritanont
Jan 30, 2010·Biochemical Pharmacology·Xiaoming WangTatiana N Nanovskaya
Mar 21, 2007·Chemistry & Biodiversity·Bernard Testa, Stefanie D Krämer
Nov 11, 2010·Journal of Veterinary Pharmacology and Therapeutics·L MatéC Lanusse
Aug 5, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Weixue HuangLong Yu
Aug 30, 2008·Chemico-biological Interactions·Martina GavelováLenka Skálová
Jun 16, 2010·Journal of Food Science·Faraj HijazJ Scott Smith
Nov 28, 2006·Life Sciences·Hideaki ShimadaYorishige Imamura
Feb 16, 2006·Toxicology Letters·Vanessa Gonzalez CovarrubiasJavier G Blanco
Jun 27, 2008·Chemico-biological Interactions·Magnus CarlquistMarie F Gorwa-Grauslund
Jan 18, 2015·Chemico-biological Interactions·Rudolf AndrýsVladimír Wsól
Oct 2, 2012·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Lucie SkarydovaVladimir Wsól
Feb 22, 2012·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Jillissa C Molnari, Alan L Myers
Apr 7, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Zidong Donna FuCurtis D Klaassen
Jan 17, 2017·Journal of Veterinary Pharmacology and Therapeutics·M L MatéG Virkel
Jul 18, 2017·Expert Opinion on Drug Metabolism & Toxicology·Sophia M Shi, Li Di
Nov 5, 2008·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yorishige Imamura
Aug 3, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Diane RamsdenMatthew A Cerny
Apr 24, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jamie N ConnarnDuxin Sun
Feb 28, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Haruka NishimutaMasashi Yabuki
Jan 21, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Stefan BlechKlaus Wagner
Feb 23, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Zeen TongJoAnn Scatina
Oct 22, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Osama Y AlshogranThomas D Nolin
Feb 25, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jian MengXiaoyan Chen
Jan 9, 2014·Pharmacological Reports : PR·Yong WuZhi-Liang Sun
Aug 5, 2017·Frontiers in Pharmacology·Xiangmeng WuYan Li
Jul 19, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Nina KassnerLeszek Wojnowski

❮ 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.