The human xenobiotic-metabolizing enzyme arylamine N-acetyltransferase 1 (NAT1) is irreversibly inhibited by inorganic (Hg2+) and organic mercury (CH3Hg+): Mechanism and kinetics

被引：9

作者：

Ragunathan, Nilusha ^{[1
]}

Busi, Florent ^{[1
,2
]}

Pluvinage, Benjamin ^{[1
,2
]}

Sanfins, Elodie ^{[1
]}

Dupret, Jean-Marie ^{[1
,2
]}

Rodrigues-Lima, Fernando ^{[1
,2
]}

Dairou, Julien ^{[1
,2
]}

机构：

[1] Univ Paris Diderot Paris 7, Unite Biol Fonct & Adaptat, CNRS, EAC 4413, F-75013 Paris, France

[2] Univ Paris Diderot Paris 7, UFR Sci Vivant, F-75013 Paris, France

来源：

FEBS LETTERS | 2010年 / 584卷 / 15期

关键词：

Xenobiotic metabolism; Arylamine N-acetyltransferase; Mercury; Inhibition; BREAST-CANCER CELLS; IN-VITRO; TOXIC METALS; N-ACETYLTRANSFERASE-1; ACETYLATION; LIVER; TARGET; GENES; LUNG;

D O I：

10.1016/j.febslet.2010.06.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 k(inact) = 1.4 x 10(4) M-1 s(-1) for Hg2+ and IC50 = 1.4 mu M and k(inact) = 2 x 10(2) M-1 s(-1) for CH3Hg+). Exposure of lung epithelial cells led to the inhibition of cellular NAT1 (IC50 = 3 and 20 mu M for Hg2+ and CH3Hg+, respectively). Our data suggest that exposure to mercury may affect the biotransformation of aromatic amines by NAT1. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：3366 / 3369

页数：4

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