ESR Investigation of Tyrosyl Radicals of Prostaglandin H Synthase; Relation to Enzyme Catalysis

Abstract

Prostaglandin H Synthase (PHS) catalyses the oxygenation of arachidonic acid to prostaglandin endoperoxides, the initial step in prostaglandin, thromboxane, and prostacyclin biosynthesis. PHS exhihits two catalytic activities, a cyclooxygenase that oxygenates arachidonic acid to a hydroperoxide and a peroxidase that reduces the hydroperoxide to an alcohol in the presence of a reducing substrate. The mechanisms by which PHS oxidizes arachidonic acids is of considerable interest. Tyrosyl radicals of PHS are produced transiently following addition of arachidonic acid or PGG₂ to the resting enzyme. In particular, it is important to determine whether their formation is essential for cyclooxygenase catalysis or reflects a side reaction that occurs concomitant with catalysis.