Evidence of a Cyclooxygenase-related Prostaglandin Synthesis in Coral

Abstract

Certain corals are rich natural sources of prostaglandins, the metabolic origin of which has remained undefined. By analogy with the lipoxygenase/allene oxide synthase pathway to jasmonic acid in plants, the presence of (8R)-lipoxygenase and allene oxide synthase in the coral Plexaura homomalla In the present study, active preparations of G. fruticosa have been used to identify both types of arachidonic acid metabolism and specific inhibitors were used to establish the enzyme type involved in the prostaglandin biosynthesis. The synthesis of prostaglandins and (11R)-hydroxyeicosatetraenoic acid was inhibited by mammalian cyclooxygenase inhibitors (indomethacin, aspirin, and tolfenamic acid), while the formation of the products of the 8-lipoxygenase/allene oxide pathway was not affected or was increased. The specific cyclooxygenase-2 inhibitor, nimesulide, did not inhibit the synthesis of prostaglandins in coral. We conclude that coral uses two parallel routes for the initial oxidation of polyenoic acids: the cyclooxygenase route, which leads to optically active prostaglandins, and the lipoxygenase/allene oxide synthase metabolism, the role of which remains to be established. An enzyme related to mammalian cyclooxygenases is the key to prostaglandin synthesis in coral. Based on our inhibitor data, the catalytic site of this evolutionary early cyclooxygenase appears to differ significantly from both known mammalian cyclooxygenases.

Prostaglandins in non-insectan invertebrates: recent insights and unsolved problems

“…Knight et al, 1999) suggesting the existence of a COX-derived mechanism for PG biosynthesis. More recent biochemical studies using the Arctic coral Gersemia fruticosa have demonstrated that radiolabelled arachidonate can be converted to the unstable intermediate PGG 2 (Varvas et al, 1999). The cDNA that codes for a COX isozyme was subsequently cloned from this coral ) and the deduced amino acid sequence of the G. fruticosa COX revealed the presence of Ile 523 that mainly confers the specificity of this enzyme towards COX inhibitors.…”

The structure of coral allene oxide synthase reveals a catalase adapted for metabolism of a fatty acid hydroperoxide

“…By analogy to the plant CYP74 P450 family that metabolize fatty acid hydroperoxides, such homologues could exhibit AOS, hydroperoxide lyase, epoxyalcohol synthase, or divinyl ether synthase activities (6). Whether residing in fusion proteins or as autonomous polypeptides, 8R-LOX and AOS activities are ubiquitous in corals (5,33,34), and their expression will likely be detected in other invertebrates (35). Other homologues of the AOS domain suggest expanded roles.…”

The origin of 15 R -prostaglandins in the Caribbean coral Plexaura homomalla : Molecular cloning and expression of a novel cyclooxygenase

“…For a time, evidence from P. homomalla and other corals suggested that prostaglandin biosynthesis occurred analogously to jasmonic acid synthesis in plants via the lipoxygenase-allene oxide route (8,(10)(11)(12). Formation of an intermediate typical to mammalian prostaglandin synthesis in coral was established through our biochemical studies on the Arctic soft coral Gersemia fruticosa (13)(14)(15). This prostaglandin-containing coral converts radiolabeled arachidonic acid to the endoperoxide intermediate PGG 2 in vitro.…”