Prostaglandin G/H synthase

Funk, C. D., Funk, L. B., Kennedy, M. E., Pong, A. S., Fitzgerald, G. A. Human platelet/erythroleukemia cell prostaglandin G/H synthase cDNA cloning, expression, and gene chromosomal assignment, FASEB J. 1991, 5, 2304-2312. 

Glaser, K., Sung, M.L., O Neil, K., Belfat, M., Hartmann, B., Carlson, R., Kreft, A., Kubrak, D., Hgio, C.L., Weichmann, B. Etodolac selectively inhibits human prostaglandin G/H synthase-2 (PGHS-2) versus human PGHS-1, Eur. J. Pharmacol. 1995, 281, 107-111. 

Young, J. M., Panah, S., Satchawatcharaphong, C., Cheung, P. S. Human whole blood assays for inhibition of prostaglandin G/H synthases-1 and -2 using A23187 and lipopolysaccharide stimulation of thromboxane B2 production, Inflamm. Res. 1996, 45, 246-253. 

Stroebel M, Goppelt-Struebe M. Signal transduction pathways responsible for serotonin-mediated prostaglandin G/H synthase expression in rat mesangial cells. J Biol Chem 1994 269 22,952-22,957. 

Chintakunta VK, Akella V, Vedula MS et aL (2002) 3-0-Substituted benzyl pyrazidone derivatives as COX inhibitors. Eur J Med Chem 37 339-347 Coleman RA, Smith WL, Narumiya S (1994) VIII. International union of pharmacology classification of prostanoid receptors Properties, distribution, and structure of the receptors and their subtypes. Pharmacol Rev 46 205-229 Copeland RA, Williams JM, Giannaras J et al. (1994) Mechanism of selective inhibition of the inducible isoform of prostaglandin G/H synthase. Proc Natl Acad Sd USA 91 11202-11206... 

Xie W, Robertson DL, Simmons DL (1992) Mitogen-inducible prostaglandin G/H synthase A new target for nonsteroidal antiinflammatory drugs. Drug Dev Res 25 249-265... 

Mancini JA, O Neill GP, Bayly C, Vickers PJ. Mutation of serine-516 in human prostaglandin G/H synthase-2 to methionine or aspirin acetylation of this residue stimulates 15-R-HETE synthesis. FEES Lett. 1994 342 33-37. 

Prostaglandin G/H synthase (cyclo-oxygen ase) (inhibited by NSAIDs)... 

Many patients who take aspirin for vascular disease may also require an NSAID for, e.g. joint disease, and it may be argued that the NSAID renders aspirin unnecessary as both act by inhibition of prostaglandin G/H synthase. As inhibition by aspirin is irreversible and that by NSAIDs may not be, continued use of aspirin in such circumstances seems prudent, especially if NSAID use is intermittent. 

Figure 1. Arachidonic acid is cleaved from membrane phospholipids by the action of phospholipase kj The liberated arachidonic acid is then acted upon by prostaglandin G/H synthase to produce the unstable intermediate PGH2. PGH2 is converted to the multiple prostanoids shown by tissue specific isomerases. The resulting prostanoids then activate cell-membrane receptor which couple G proteins leading to the terminal effect designated in each of the boxes (with permission from [8]).

Iq25.2-q25.3 8.62 PTGS2 Prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) 600262 ... 

Prostaglandin G/H synthase, which is able to use a number of xenobiotics as cofactors in a cooxidation reaction. 

Kargman SL, O Neill GP, Vickers PJ, Evans JF, Mancini JA, Jothy S. Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. Cancer Res. 55 (1995) 2556-2559. 

An important fate of arachidonic acid is enzymatic conversion to prostaglandins by one of two prostaglandin G/H synthases [23]. As described in Chapter 12, these enzymes have... 

Arachidonic acid, which is stored as a cellular membrane phospholipid, is the precursor for series 2 prostaglandins. Aspir in selectively acetylates the hydroxyl group of a single serine residue at position 530 within the polypeptide chain of prostaglandin G/H synthase, the enzyme that converts arachidonate into prostaglandin cyclic endoperoxide. Aspirin thereby reduces the synthesis of the eicosanoids— prostaglandins, prostacyclin, and thromboxane A. 

AA is metabolized successively to the cyclic endoperoxide prostaglandins G (PGG) and H (PGH) (Figure 25—1) by the cyclooxygenase (COX) and hydroperoxidase (HOX) activities of the prostaglandin G/H synthases. Isomerases and synthases effect the transformation of PGH2 into terminal prostanoids distinguished by substitutions on their cyclopentane rings. 

INHIBITION OF PROSTAGLANDIN BIOSYNTHESIS BY NSAIDS The first enzyme in the prostaglandin synthetic pathway is prostaglandin G/H synthase, also known as COX. This enzyme converts arachidonic acid (AA) to the unstable intermediates PGGj and PGH and leads to the production of thromboxane A (TXA ) and a variety of prostaglandins (see Chapter 25). 

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