Fatty acid binding to cyclooxygenases

Abstract

Prostaglandin endoperoxide H synthase-1 and -2 (PGHS-1 and -2) convert arachidonic acid (AA) to prostaglandin H 2 (PGH 2) in the committed step in prostaglandin biosynthesis. Although the cyclooxygenase activity favors AA as the substrate, both isoforms will oxygenate a variety of 18–22 carbon fatty acids with reduced efficiencies. In this review, we discuss how the fatty acid substrates AA and dihomo-γ-linolenic acid (DHLA; 20:3 ω−6) are bound in the cyclooxygenase active site of ovine (o) PGHS-1. Based on the conformations of the fatty acids within the active site, we describe the key roles that Val349 and Ser530 play as determinants of fatty acid substrate specificity for oPGHS-1.