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

FEBS Lett. 2010 Aug 4;584(15):3366-9. doi: 10.1016/j.febslet.2010.06.022. Epub 2010 Jun 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl Coenzyme A / pharmacology
  • Arylamine N-Acetyltransferase / antagonists & inhibitors*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects
  • Epithelial Cells / enzymology
  • Glutathione / pharmacology
  • Humans
  • Isoenzymes / antagonists & inhibitors*
  • Kinetics
  • Lung / cytology
  • Mercury / pharmacology*
  • Methylmercury Compounds / pharmacology*
  • Xenobiotics / metabolism*


  • Isoenzymes
  • Methylmercury Compounds
  • Xenobiotics
  • Acetyl Coenzyme A
  • Arylamine N-Acetyltransferase
  • N-acetyltransferase 1
  • Mercury
  • Glutathione