Prostaglandin G2

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Prostaglandin G2
2D structure for Prostaglandin G2
Chemical Name	(E)-7-[(1S,2R,3S,4R)-3-[(E,3S)-3-hydroperoxyoct-1-enyl]-5,6-dioxabicyclo[2.2.1]hept-2-yl]hept-5-enoic acid
Chemical Formula	C₂₀H₃₂O₆
CAS Number	51982-36-6
Chemical Information	HMDB03235
Biochemical Taxonomy	Prostanoids
Functional Taxonomy	Not Available
Nutritional Taxonomy	Not Available
Metabolic Pathways	Not Available
Biofluid Location	Not Available
Tissue Location	Not Available
Normal Biofluid Concentrations	Not Available
Normal Tissue Concentrations	Not Available
Diseases / Conditions Related to Nutrition	Not Available
Other (Monogenic Disorders)	Not Available
Abnormal Biofluid Concentrations	Not Available
Abnormal Tissue Concentrations	Not Available
Physiological Processes	Not Available

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Introduction

guidelines
Prostaglandin G2 (PGG2) is synthesized from arachidonic acid on a cyclooxygenase (COX) metabolic pathway as a primary step; the COX biosynthesis of prostaglandin (PG) begins with the highly specific oxygenation of arachidonic acid in the 11R configuration and ends with a 15S oxygenation to form PGG2. The COX site activity that catalyzes the conversion of arachidonic acid to PGG2 is the target for nonsteroidal antiinflammatory drugs (NSAIDs). The peroxidase site activity catalyzes the two-electron reduction of the hydroperoxide bond of PGG2 to yield the corresponding alcohol prostaglandin H2 (PGH2). The formation of a phenoxyl radical on Tyr385 couples the activities of the two sites. The Tyr385 radical is produced via oxidation by compound I, an oxoferryl porphyrin -cation radical, which is generated by reaction of the hemin resting state with PGG2 or other hydroperoxides. The tyrosyl radical homolytically abstracts the 13proS hydrogen atom of arachidonic acid which initiates a radical cascade that ends with the stereoselective formation of PGG2. PGG2 then migrates from the cyclooxygenase (COX) site to the peroxidase (POX) site where it reacts with the hemin group to generate PGH2 and compound I. The heterolytic oxygen-oxygen bond cleavage is assisted by the conserved distal residues His207 and Gln203, mutation of which has been shown to severely impair enzyme activity. Compound I, upon reaction with Tyr385, gives compound II, which in turn is reduced to the hemin resting state by one-electron oxidation of reducing cosubstrates or undergoes reactions that result in enzyme self-inactivation. Prostaglandin endoperoxide H synthase (PGHS) 1 is a bifunctional membrane enzyme of the endoplasmic reticulum that converts arachidonic acid into prostaglandin H2 (PGH2), the precursor of all prostaglandins, thromboxanes, and prostacyclins. These lipid mediators are intricately involved in normal physiology, namely, in mitogenesis, fever generation, pain response, lymphocyte chemotaxis, fertility, and contradictory stimuli such as vasoconstriction and vasodilatation, as well as platelet aggregation and quiescence. PGHS is implicated in numerous pathologies, including inflammation, cancers of the colon, lung, and breast, Alzheimer's disease, Parkinson's disease, and numerous cardiovascular diseases including atherosclerosis, thrombosis, myocardial infarction, and stroke. (PMID: 14594816, 16552393, 16411757)