Snapshot of the cyclooxygenase reaction pathway: Structure of prostaglandin at the active site of COX-2

Prostaglandin (PG) H synthases (PGHS) or cyclooxygenases (COX) catalyse the peroxidation of arachidonic acid (AA) to PGG2 and PGH2 which are further converted to a series of prostaglandins and thromboxane A2. Here, we report that GSH promotes concomitant formation of the current oxidative stress biomarkers malondialdehyde (MDA) and 15(S)-8-iso-prostaglandin F2α from AA via PGHS. This illustrates an uncommon interplay of enzymatic and chemical reactions to produce species that are considered to be exclusively produced by free-radical-catalysed reactions. We propose mechanisms for the PGHS/AA/GSH-dependent formation of MDA, 15(S)-8-iso-prostaglandin F2α and other F2-isoprostanes. These mechanisms are supported by clinical observations.