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 (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.