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The human xenobiotic‐metabolizing enzyme arylamine N ‐acetyltransferase 1 (NAT1) is irreversibly inhibited by inorganic (Hg 2+ ) and organic mercury (CH 3 Hg + ): Mechanism and kinetics
Author(s) -
Ragunathan Nilusha,
Busi Florent,
Pluvinage Benjamin,
Sanfins Elodie,
Dupret Jean-Marie,
Rodrigues-Lima Fernando,
Dairou Julien
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.06.022
Subject(s) - chemistry , biotransformation , mercury (programming language) , arylamine n acetyltransferase , xenobiotic , enzyme , n acetyltransferase , amine gas treating , aromatic amine , stereochemistry , cysteine , medicinal chemistry , biochemistry , organic chemistry , acetylation , computer science , gene , programming language
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 (Hg 2+ ) and organic (CH 3 Hg + ) mercury inhibit the biotransformation functions of NAT1. Both compounds react irreversibly with the active‐site cysteine of NAT1 (half‐maximal inhibitory concentration (IC 50 ) = 250 nM and k inact = 1.4 × 10 4 M −1 s −1 for Hg 2+ and IC 50 = 1.4 μM and k inact = 2 × 10 2 M −1 s −1 for CH 3 Hg + ). Exposure of lung epithelial cells led to the inhibition of cellular NAT1 (IC 50 = 3 and 20 μM for Hg 2+ and CH 3 Hg + , respectively). Our data suggest that exposure to mercury may affect the biotransformation of aromatic amines by NAT1.