Molecular basis for deficient acetaminophen glucuronidation in cats. An interspecies comparison of enzyme kinetics in liver microsomes

Biochemical Pharmacology
M H Court, D J Greenblatt

Abstract

Cats are highly susceptible to acetaminophen toxicity because of deficient glucuronidation of this drug in vivo. The enzyme kinetic basis for this defect is unknown. Therefore, the kinetic properties of acetaminophen UDP-glucuronosyltransferase (acetaminophen-UGT) were investigated, using hepatic microsomes from cats (N = 4) compared with those of species that are less sensitive to acetaminophen intoxication including dogs (N = 4), humans (N = 4), and six other mammalian species (one liver from each). Gunn rats were also studied, since they express defective UGT family 1 isoenzymes and are also prone to acetaminophen toxicity. Acetaminophen kinetics were biphasic in all instances with distinct high and low affinity components. Km values for the high affinity activity in cat microsomes (0.31 +/- 0.1 mM; mean +/- SEM) were intermediate between those of dogs (0.11 +/- 0.02 mM) and humans (0.60 +/- 0.06 mM) and other species (0.22 to 6.7 mM; range). On the other hand, high affinity Vmax values were over 10-fold less in cat microsomes (0.025 +/- 0.006 nmol/min/mg) than in dogs (0.92 +/- 0.09 nmol/min/mg) and humans (0.27 +/- 0.09 nmol/min/mg); and over 5-fold less compared with microsomes from other species (range 0.13 to 7.63 nmol/...Continue Reading

References

Aug 1, 1977·Annals of Internal Medicine·B Ameer, D J Greenblatt
Apr 1, 1978·Journal of Pharmacokinetics and Biopharmaceutics·K YamaokaT Uno
Jan 1, 1992·Drug Metabolism Reviews·N P VermeulenR Van de Straat
Jan 1, 1972·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·I D CapelR T Williams
Oct 1, 1974·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·I D CapelR T Williams
Jun 15, 1984·Toxicology and Applied Pharmacology·M C SavidesH W Leipold
Aug 1, 1994·British Journal of Clinical Pharmacology·T AnderssonD J Birkett
Mar 1, 1993·Biopharmaceutics & Drug Disposition·L L von MoltkeD J Greenblatt
Dec 1, 1996·Human & Experimental Toxicology·M Dickins, M K Bayliss

❮ Previous
Next ❯

Citations

Dec 23, 2006·Analytical and Bioanalytical Chemistry·J L C M DorneA M J Ragas
Dec 29, 2010·Journal of Molecular Evolution·Tamara SchenekarSteven Weiss
May 18, 2005·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Yan FengRaman Venkataramanan
Aug 5, 2008·Journal of Feline Medicine and Surgery·Sheilah A RobertsonBenedict Duncan X Lascelles
Dec 7, 2000·Journal of Veterinary Pharmacology and Therapeutics·E CastroO Tapia
Jun 17, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Sarah N CampionJosé E Manautou
May 29, 2014·American Journal of Veterinary Research·David Sanchez-Migallon GuzmanJoanne R Paul-Murphy
Apr 14, 2006·Journal of the American Animal Hospital Association·Adam D GasselSherry K Cox
Dec 13, 2006·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·H WongD D Christ
Dec 25, 2015·Environmental Science & Technology·Weihong GuoJune-Soo Park
Mar 27, 2007·The Journal of Small Animal Practice·H M SymeJ Elliott
Sep 7, 2007·Journal of Veterinary Pharmacology and Therapeutics·C LainesseM Doucet
Mar 1, 2008·Journal of Veterinary Pharmacology and Therapeutics·L S Slingsby, P M Taylor
Jun 1, 2006·Veterinary and Comparative Oncology·S H Tannehill-GreggT J Rosol
Nov 11, 2010·Journal of Veterinary Pharmacology and Therapeutics·C D van BeusekomJ Fink-Gremmels
Feb 18, 2011·Journal of Veterinary Pharmacology and Therapeutics·K T SiaoJ E Ilkiw
Apr 11, 2012·Journal of Veterinary Pharmacology and Therapeutics·T EbnerJ Elliott
Jul 31, 2013·Journal of Veterinary Pharmacology and Therapeutics·C D van BeusekomJ A Schrickx
Nov 14, 2006·Life Sciences·Nagako TanakaHiroshi Yokota
Dec 4, 2014·European Journal of Drug Metabolism and Pharmacokinetics·Abby C CollierClaire E Kendal-Wright
Oct 27, 2004·Journal of Veterinary Pharmacology and Therapeutics·K WegnerW W Muir
Oct 7, 2005·Journal of Veterinary Pharmacology and Therapeutics·S A RobertsonJ W Sear
Jun 10, 2015·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Jessica LawrenceDavid Argyle
Dec 20, 2014·New Zealand Veterinary Journal·R VillaP Cagnardi
Jun 21, 2001·The Veterinary Journal·E F CastroM O Tapia
Oct 16, 2016·Bulletin of Environmental Contamination and Toxicology·Esmarie Boyles, Clayton K Nielsen
Jan 4, 2005·The Veterinary Clinics of North America. Small Animal Practice·Sheilah A Robertson
Jul 25, 2006·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Zaher A Radi, Nasir K Khan
Feb 28, 2017·Integrated Environmental Assessment and Management·Esmarie Boyles, Clayton K Nielsen
Sep 21, 2012·Journal of Feline Medicine and Surgery·Paulina HaroAmalia Agut
Nov 5, 2014·Journal of Feline Medicine and Surgery·Ingrid van HoekVincent Biourge
Sep 15, 2004·Journal of Feline Medicine and Surgery·P M Taylor, S A Robertson
Jan 17, 2012·Journal of Feline Medicine and Surgery·David BennettPamela Johnston
Feb 24, 2009·Toxicologic Pathology·Zaher A Radi
Dec 2, 2015·Journal of Feline Medicine and Surgery·Agustina AnsónAmalia Agut
May 10, 2019·Journal of Feline Medicine and Surgery·Diego Rodrigo-Mocholi, Fernando Martinez-Taboada
Jun 25, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Shringi SharmaRaman Venkataramanan

❮ 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.