Glucuronidation of Acetaminophen Catalyzed by Multiple Rat Phenol UDP-Glucuronosyltransferases

• Published in: Drug metabolism and disposition Vol. 30; no. 3; pp. 324 - 330
• Main Authors: KESSLER, Fay K, KESSLER, Marissa R, AUYEUNG, Diana J, RITTER, Joseph K
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.03.2002
• Subjects: Acetaminophen - adverse effects; Acetaminophen - metabolism; Analgesics; Analgesics - adverse effects; Analgesics - metabolism; Animals; Biological and medical sciences; Blotting, Western; Catalysis; Cells, Cultured; Chromatography, High Pressure Liquid; Enzyme Induction; Glucuronosyltransferase - biosynthesis; Glucuronosyltransferase - genetics; Glucuronosyltransferase - metabolism; Hepatocytes - metabolism; Humans; In Vitro Techniques; Kinetics; Male; Medical sciences; Microsomes, Liver - enzymology; Molecular Sequence Data; Neuropharmacology; Pharmacology. Drug treatments; Pyrazines - pharmacology; Rats; Rats, Gunn; Rats, Sprague-Dawley; Recombinant Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Rat; UDP-glucuronosyltransferase; Enzyme; Digestive system; Isozyme; Transferases; Liver; Glycosyltransferases; Rodentia; Glucuronic acid conjugation; Gene expression; Metabolism; Vertebrata; Paracetamol; Phenol; Mammalia; Analgesic; Hepatocyte; Animal; Hexosyltransferases

Gunn rats glucuronidate acetaminophen (APAP) at reduced rates and show increased susceptibility to APAP-induced hepatotoxicity. This defect is presumed to involve UDP-glucuronosyltransferase (UGT) 1A6, which is nonfunctional in Gunn rats, but it is currently unclear whether other 1A family members a...