Editing Prostaglandin (section)

=== Release of prostaglandins from the cell ===
Prostaglandins were originally believed to leave the cells via passive diffusion because of their high lipophilicity. The discovery of the [[prostaglandin transporter]] (PGT, SLCO2A1), which mediates the cellular uptake of prostaglandin, demonstrated that diffusion alone cannot explain the penetration of prostaglandin through the cellular membrane. The release of prostaglandin has now also been shown to be mediated by a specific transporter, namely the [[multidrug resistance protein 4]] (MRP4, ABCC4), a member of the [[ATP-binding cassette transporter]] superfamily. Whether MRP4 is the only transporter releasing prostaglandins from the cells is still unclear.{{citation needed|date=January 2024}}

==== Cyclooxygenases ====
Prostaglandins are produced following the sequential oxygenation of arachidonic acid, DGLA or EPA by [[cyclooxygenase]]s (COX-1 and COX-2) and terminal prostaglandin syntheses. The classic dogma is as follows:
* [[COX-1]] is responsible for the baseline levels of prostaglandins.
* [[COX-2]] produces prostaglandins through stimulation.

However, while COX-1 and COX-2 are both located in the [[blood vessels]], [[stomach]] and the [[kidneys]], prostaglandin levels are increased by COX-2 in scenarios of [[inflammation]] and [[Human development (biology)|growth]].

==== Prostaglandin E synthase ====
[[Prostaglandin E2|Prostaglandin E<sub>2</sub>]] (PGE<sub>2</sub>) — the most abundant prostaglandin<ref>{{cite journal | vauthors = Ke J, Yang Y, Che Q, Jiang F, Wang H, Chen Z, Zhu M, Tong H, Zhang H, Yan X, Wang X, Wang F, Liu Y, Dai C, Wan X | title = Prostaglandin E2 (PGE2) promotes proliferation and invasion by enhancing SUMO-1 activity via EP4 receptor in endometrial cancer | journal = Tumour Biology | volume = 37 | issue = 9 | pages = 12203–12211 | date = September 2016 | pmid = 27230680 | pmc = 5080328 | doi = 10.1007/s13277-016-5087-x | quote = Prostaglandin E2 (PGE2) is the most abundant prostanoid in the human body }}</ref> — is generated from the action of [[prostaglandin E synthase]]s on prostaglandin H<sub>2</sub> ([[prostaglandin H2]], PGH<sub>2</sub>). Several prostaglandin E syntheses have been identified.  To date, microsomal (named as [[misoprostol]]) prostaglandin E synthase-1 emerges as a key enzyme in the formation of PGE<sub>2</sub>.{{citation needed|date=January 2024}}

==== Other terminal prostaglandin synthases ====
Terminal prostaglandin syntheses have been identified that are responsible for the formation of other prostaglandins. For example, hematopoietic and [[lipocalin]] [[prostaglandin D synthase]]s (hPGDS and lPGDS) are responsible for the formation of [[PGD2|PGD<sub>2</sub>]] from PGH<sub>2</sub>. Similarly, prostacyclin (PGI<sub>2</sub>) synthase (PGIS) converts PGH<sub>2</sub> into PGI<sub>2</sub>. A thromboxane synthase ([[thromboxane-A synthase|TxAS]]) has also been identified.
[[Prostaglandin-F synthase]] (PGFS) catalyzes the formation of 9α,11β-PGF<sub>2α,β</sub> from PGD<sub>2</sub> and PGF<sub>2α</sub> from PGH<sub>2</sub> in the presence of NADPH. This enzyme has recently been crystallized in complex with PGD<sub>2</sub><ref>{{cite journal | vauthors = Komoto J, Yamada T, Watanabe K, Takusagawa F | title = Crystal structure of human prostaglandin F synthase (AKR1C3) | journal = Biochemistry | volume = 43 | issue = 8 | pages = 2188–98 | date = March 2004 | pmid = 14979715 | doi = 10.1021/bi036046x }}</ref> and bimatoprost<ref>{{cite journal | vauthors = Komoto J, Yamada T, Watanabe K, Woodward DF, Takusagawa F | title = Prostaglandin F2alpha formation from prostaglandin H2 by prostaglandin F synthase (PGFS): crystal structure of PGFS containing bimatoprost | journal = Biochemistry | volume = 45 | issue = 7 | pages = 1987–96 | date = February 2006 | pmid = 16475787 | doi = 10.1021/bi051861t }}</ref> (a synthetic analogue of PGF<sub>2α</sub>).