title: Prostaglandin H synthases: members of a class of quasi-linear threshold switches.
abstract: Prostaglandin H synthase (PTGS or COX) enzymes catalyze rate-limiting steps in the synthesis of potent prostanoids, including various prostaglandins, thromboxane, and prostacyclin. Mechanisms that have evolved for regulating prostanoid biosynthesis reflect a tension between achieving a rapid but measured response to cellular signals while minimizing spurious activation by signal noise. We found through mathematical modeling that the PTGS enzymes can be thought of as regulatory switches with approximately linear output above an adjustable threshold. In vivo synthesis allows continuous production while signal remains above threshold. Different isoforms show specific adaptions reflecting their physiological roles as constitutive or inducible enzymes. Mathematical modeling helps explain how these adaptations enable the PTGS1 and PTGS2 enzymes to maintain their physiological roles while avoiding potentially damaging consequences.
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M2 B500 Seattle, WA 98109-1024, USA. hazelton@fhcrc.org
authors.forename: William D
authors.initials: WD
authors.lastname: Hazelton
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Tien
authors.forename: Vinsunt W
authors.initials: VW
authors.lastname: Donato
authors.forename: Rachel
authors.initials: R
authors.lastname: Sparks
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Ulrich
mesh_terms: D007700:Kinetics; D008954:Models, Biological; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry / Q000145:classification* / Q000378:metabolism
chemical_list: D011451:Prostaglandin-Endoperoxide Synthases