Cyclooxygenases: Structural, Cellular, and Molecular Biology

Annu Rev Biochem. 2000;69:145-82. doi: 10.1146/annurev.biochem.69.1.145.

Abstract

The prostaglandin endoperoxide H synthases-1 and 2 (PGHS-1 and PGHS-2; also cyclooxygenases-1 and 2, COX-1 and COX-2) catalyze the committed step in prostaglandin synthesis. PGHS-1 and 2 are of particular interest because they are the major targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin, ibuprofen, and the new COX-2 inhibitors. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. In this review, we examine how the structures of these enzymes relate mechanistically to cyclooxygenase and peroxidase catalysis, and how differences in the structure of PGHS-2 confer on this isozyme differential sensitivity to COX-2 inhibitors. We further examine the evidence for independent signaling by PGHS-1 and PGHS-2, and the complex mechanisms for regulation of PGHS-2 gene expression.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Catalysis
  • Cyclooxygenase Inhibitors / pharmacology
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Kinetics
  • Models, Molecular
  • Peroxidases / chemistry
  • Peroxidases / genetics
  • Peroxidases / metabolism
  • Prostaglandin-Endoperoxide Synthases / chemistry*
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Peroxidases
  • Prostaglandin-Endoperoxide Synthases