The human xenobiotic-metabolizing enzyme arylamine N-acetyltransferase 1 (NAT1) is irreversibly inhibited by inorganic (Hg) and organic mercury (CH3Hg): Mechanism and kinetics |
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| Authors: | Nilusha Ragunathan Benjamin Pluvinage Elodie Sanfins Fernando Rodrigues-Lima Julien Dairou |
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| Institution: | a Univ Paris Diderot-Paris 7, Unité de Biologie Fonctionnelle et Adaptative, CNRS EAC 4413, 75013 Paris, France
b UFR des Sciences du Vivant, Univ Paris Diderot-Paris 7, 75013 Paris, France |
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| 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 = 1.4 × 104 M−1 s−1 for Hg2+ and IC50 = 1.4 μM and kinact = 2 × 102 M−1 s−1 for CH3Hg+). Exposure of lung epithelial cells led to the inhibition of cellular NAT1 (IC50 = 3 and 20 μM for Hg2+ and CH3Hg+, respectively). Our data suggest that exposure to mercury may affect the biotransformation of aromatic amines by NAT1. |
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| Keywords: | NAT arylamine N-acetyltransferase NAT1 human arylamine N-acetyltransferase 1 XME xenobiotic-metabolizing enzyme IC50 half-maximal inhibitory concentration PNPA p-nitrophenylacetate PAS p-aminosalicylate |
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