title: The human xenobiotic-metabolizing enzyme arylamine N-acetyltransferase 1 (NAT1) is irreversibly inhibited by inorganic (Hg2+) and organic mercury (CH3Hg+): mechanism and kinetics.
abstract: Human arylamine N-acetyltransferase 1 (NAT1) is a xenobiotic-metabolizing enzyme that biotransforms aromatic amine chemicals. We show here that biologically-relevant concentrations of inorganic (Hg2+) and organic (CH3Hg+) mercury inhibit the biotransformation functions of NAT1. Both compounds react irreversibly with the active-site cysteine of NAT1 (half-maximal inhibitory concentration (IC50)=250 nM and kinact=1.4x10(4) M(-1) s(-1) for Hg2+ and IC50=1.4 microM and kinact=2x10(2) M(-1) s(-1) for CH3Hg+). Exposure of lung epithelial cells led to the inhibition of cellular NAT1 (IC50=3 and 20 microM for Hg2+ and CH3Hg+, respectively). Our data suggest that exposure to mercury may affect the biotransformation of aromatic amines by NAT1.
authors.affiliation: University of Paris Diderot-Paris 7, Unité de Biologie Fonctionnelle et Adaptative, CNRS EAC 4413, 75013 Paris, France.
authors.forename: Nilusha
authors.initials: N
authors.lastname: Ragunathan
authors.forename: Florent
authors.initials: F
authors.lastname: Busi
authors.forename: Benjamin
authors.initials: B
authors.lastname: Pluvinage
authors.forename: Elodie
authors.initials: E
authors.lastname: Sanfins
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Dupret
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodrigues-Lima
authors.forename: Julien
authors.initials: J
authors.lastname: Dairou
mesh_terms: D000105:Acetyl Coenzyme A / Q000494:pharmacology; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008168:Lung / Q000166:cytology; D008628:Mercury / Q000494:pharmacology*; D008767:Methylmercury Compounds / Q000494:pharmacology*; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D008767:Methylmercury Compounds; D015262:Xenobiotics; D000105:Acetyl Coenzyme A; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; D008628:Mercury; D005978:Glutathione