A metabolite of acetaminophen covalently binds to the 56 kDa selenium binding protein

Biochem Biophys Res Commun. 1992 Feb 14;182(3):1348-55. doi: 10.1016/0006-291x(92)91881-p.

Abstract

Acetaminophen is metabolized by cytochrome P450 to a reactive metabolite that covalently binds to proteins and this binding correlates with the hepatotoxicity. The major protein adduct was previously reported to be a 55 kDa protein that was detected on Western blots using antisera specific for 3-(cystein-S-yl)acetaminophen. In this study, the 55 kDa protein was isolated using a combination of ion exchange fast flow chromatography, hydroxyapatite HPLC and anion exchange HPLC. Amino acid sequences of 8 internal peptides from a trypsin digestion of the 55 kDa protein were found to have 97% homology with the deduced amino acid sequence from a cDNA that corresponds to a 56 kDa selenium binding protein. This is the first report of a specific protein to which a metabolite of acetaminophen covalently binds.

Publication types

  • Comparative Study

MeSH terms

  • Acetaminophen / analogs & derivatives*
  • Acetaminophen / metabolism*
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Biotransformation
  • Carrier Proteins / genetics
  • Carrier Proteins / isolation & purification
  • Carrier Proteins / metabolism*
  • Cell Fractionation
  • Chromatography, High Pressure Liquid
  • Chromatography, Ion Exchange
  • Cytosol / metabolism
  • Immune Sera
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • Molecular Weight
  • Peptide Fragments / isolation & purification
  • Selenium / isolation & purification
  • Selenium / metabolism*
  • Selenium-Binding Proteins
  • Sequence Homology, Nucleic Acid
  • Ultrafiltration

Substances

  • Carrier Proteins
  • Immune Sera
  • Peptide Fragments
  • Selenbp1 protein, mouse
  • Selenbp2 protein, mouse
  • Selenium-Binding Proteins
  • Acetaminophen
  • 3-(cystein-S-yl)paracetamol
  • Selenium