Prostaglandin H Synthase: Perturbation of the Tyrosyl Radical as a Probe of Anti-Cyclooxygenase Agents

  • Richard J. Kulmacz
  • Graham Palmer
  • Ah-Lim Tsai
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

Prostaglandin H synthase exhibits two distinct catalytic activities. A cyclooxygenase activity that incorporates two molecules of molecular oxygen into arachidonic acid to form prostaglandin (PG) G2, and a rather nonspecific heme-dependent peroxidase that reduces hydoperoxides (e.g. PGG2) to the corresponding alcohols (e.g. PGH2) at the expense of an electron donor. The conversion of arachidonate to PGG2 in the cyclooxygenase reaction is believed to proceed via a free radical reaction mechanism that is initiated by the abstraction of a hydrogen atom from C13 of the fatty acid to form a fatty acyl free radical (Hamberg and Samuelsson, 1967). Rearrangement of the fatty acyl backbone and attack on molecular oxygen follow in a concerted fashion to give PGG2. The role of the synthase in this conversion is presumably to furnish the oxidant necessary for abstraction of the C13 hydrogen atom, and to bind the fatty acid in an arrangement that determines the stereochemical outcome. The identity of the enzyme oxidant responsible is a key question in the study of the cyclooxygenase catalytic mechanism.

Keywords

Cyclooxygenase Activity Prostaglandin Endoperoxide Tyrosyl Radical Tyrosyl Residue Tyrosine Radical 
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

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Richard J. Kulmacz
    • 1
  • Graham Palmer
    • 2
  • Ah-Lim Tsai
    • 1
  1. 1.Division of Hematology and OncologyUniversity of Texas Health Science Center at HoustonHoustonUSA
  2. 2.Department of Biochemistry and Cell BiologyRice UniversityHoustonUSA

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