PGE Synthase

Prostaglandin E synthase (or PGE synthase) is an enzyme involved in eicosanoid and glutathione metabolism, a member of MAPEG family. It generates prostaglandin E (PGE) from prostaglandin H2.

PGS-IN-1
102271-49-8
1033836-12-2
HPGDS-inhibitor-1
1033836-12-2
1221971-47-6
PF 9184
1221971-47-6
1234708-04-3
SAR191801
1234708-04-3
40828-46-4
Suprofen
40828-46-4
5104-49-4
Flurbiprofen
5104-49-4
52549-17-4
Pranoprofen
52549-17-4
64092-48-4
Zomepirac Sodium
64092-48-4
B0084-292497
Mesalamine
89-57-6

Background


An Overview of PGE Synthase

Prostaglandin E2 synthase (or PGE synthase) is a terminal synthetase in the prostaglandin E2 (PGE2) synthesis pathway. PGE synthase has a variety of biological activities and participates in various pathophysiological processes. PGE synthase is produced by three consecutive enzymatic reactions. Phospholipase A2 (PLA2) catalyzes the membrane phospholipids to form arachidonic acid (AA). AA is converted to unstable prostaglandin H2 (PGH2) by the action of cyclooxygenase (COX). Finally, prostaglandin E synthase isomerized PGH2 to PGE2.

Major type of PGE Synthase

There are at least three PGE synthases having been found: cytosolic PGE2 synthase (cPGES), membrane-associated PGE2 synthase 1 (mPGES1), and membrane-associated PGE2 synthase 2 (mPGES2). cPGES is a structural enzyme widely expressed in various cells and tissues. It mainly participates in transient response to produce PGE2 together with COX-1, and maintains the stability of the intracellular environment. mPGES1 is an inducible enzyme that, together with COX-2, participates in delayed PGE2 production and is involved in a variety of pathophysiological processes. The structural and physiological functions of mPGES2 still require further study.

Inhibition of PGE Synthase

At present, COX-2 is mainly used as a target for anti-inflammatory and analgesic. Selective COX-2 inhibitors reduce gastrointestinal damage. Selective COX-2 inhibitors also block the production of PGI2, PGD2 and TXA2 while inhibiting the production of PGE2, thereby affecting the secretion of sodium, causing an increase in edema and blood pressure. It is also possible to increase the risk of thrombosis by changing the vascular tone. Therefore, people tend to find a safer and more ideal intervention.

PGE Synthase and diseases

cPGES is widely expressed in various tissues and cells, and stimulation of inflammatory factors has no effect on its expression, except that the expression level of cPGES is increased by 7-fold when the rat brain is stimulated. cPGES is mainly present in the cytoplasm. When stimulated by Ca2+, cPGES moves to the endoplasmic reticulum. cPGES converts PGH2 produced by COX-1 but not COX-2 into PGE2 in cells. cPGES and COX-1 together form an instantaneous PGE2 generation pathway. As a terminal enzyme for PGE synthesis, mPGES1 may be an ideal new target for the treatment and prevention of inflammation, osteoporosis and even cancers.

Reference:

Jakobsson P.J., Thoren S., Morgenstern R., et al. (1999) Identification of human prostaglandin E synthase: a microsomal glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Nat Acad Sci USA, 96(13): 7220.