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Acetaminophen as a Cosubstrate and Inhibitor of Prostaglandin H Synthase

  • Peter J. Harvison
  • R. W. Egan
  • P. H. Gale
  • Sidney D. Nelson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 197)

Abstract

Recently, several reports (Marnett et al., 1983; Nordenskjöld et al., 1984) have implicated prostaglandin H synthase (PHS) in the bioactivation of xenobiotics to potentially toxic metabolites. Benzidine (Zenser et al., 1983), p-aminophenol (Josephy et al., 1983), and phenacetin (Andersson et al., 1982) are among the compounds known to undergo metabolic activation by PHS. Of particular interest to us is the fact that this enzyme can metabolize acetaminophen (APAP) to a reactive species that can bind to proteins or form a glutathione conjugate (Moldeus and Rahimtula, 1980; Boyd and Eling, 1981; Mohandas et al., 1981; Moldeus et al., 1982). In fact, it has been suggested (Boyd and Eling, 1981; Mohandas et al., 1981) that the nephrotoxicity sometimes associated with APAP overdosage may be due in part to its metabolism by PHS which is present in high levels in the renal inner medulla.

Keywords

Electron Spin Resonance Arachidonic Acid Glutathione Conjugate Prostaglandin Synthetase APAP Overdosage 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Peter J. Harvison
    • 1
  • R. W. Egan
    • 2
  • P. H. Gale
    • 2
  • Sidney D. Nelson
    • 1
  1. 1.Department of Medicinal ChemistryBG-20 University of WashingtonSeattleUSA
  2. 2.Merck Institute for Therapeutic ResearchRahwayUSA

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