title: Coupling between cyclooxygenases and terminal prostanoid synthases.
abstract: Biosynthesis of prostanoids is regulated by three sequential enzymatic steps, namely phospholipase A2, cyclooxygenase (COX), and terminal prostanoid synthase. Recent evidence suggests that lineage-specific terminal prostanoid synthases, including prostaglandin (PG) E2, PGD2, PGF2alpha, PGI2, and thromboxane synthases, show distinct functional coupling with upstream COX isozymes, COX-1 and COX-2. This can account, at least in part, for segregated utilization of the two COX isozymes in distinct phases of PG-biosynthetic responses. In terms of their localization and COX preference, terminal prostanoid synthases are classified into three categories: (i) the perinuclear enzymes that prefer COX-2, (ii) the cytosolic enzyme that prefers COX-1, and (iii) the translocating enzyme that utilizes both COXs depending on the stimulus. Additionally, altered supply of arachidonic acid by phospholipase A2s significantly affects the efficiency of COX-terminal prostanoid synthase coupling. In this review, we summarize our recent understanding of the coupling profiles between the two COXs and various terminal prostanoid synthases.
authors.affiliation: Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Ueno
authors.forename: Yui
authors.initials: Y
authors.lastname: Takegoshi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kamei
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kudo
authors.forename: Makoto
authors.initials: M
authors.lastname: Murakami
mesh_terms: D000818:Animals; D051545:Cyclooxygenase 1 / Q000737:chemistry* / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000502:physiology; D011453:Prostaglandins / Q000096:biosynthesis*
chemical_list: D007527:Isoenzymes; D011453:Prostaglandins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2