Prostaglandin H2

Prostaglandin H₂ (PGH₂), or prostaglandin H2 (PGH2), is a type of prostaglandin and a precursor for many other biologically significant molecules. It is synthesized from arachidonic acid in a reaction catalyzed by a cyclooxygenase enzyme.^[2] The conversion from arachidonic acid to prostaglandin H₂ is a two-step process. First, COX-1 catalyzes the addition of two free oxygens to form the 1,2-dioxane bridge and a peroxide functional group to form prostaglandin G₂ (PGG₂).^[3] Second, COX-2 reduces the peroxide functional group to a secondary alcohol, forming prostaglandin H₂. Other peroxidases like hydroquinone have been observed to reduce PGG₂ to PGH₂.^[4] PGH₂ is unstable at room temperature, with a half life of 90–100 seconds,^[1] so it is often converted into a different prostaglandin.

Eicosanoid synthesis - prostaglandin H₂ near center

Prostaglandin H₂^[1]

Names
Other names PGH2, Endoperoxide H2, Prostaglandin R2
Identifiers
CAS Number	42935-17-1 Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:15554 Y
ChemSpider	392800 Y
IUPHAR/BPS	4483
MeSH	Prostaglandin+H2
PubChem CID	445049
UNII	J670X3LRU2 Y
CompTox Dashboard (EPA)	DTXSID80903949
InChI InChI=1S/C20H32O5/c1-2-3-6-9-15(21)12-13-17-16(18-14-19(17)25-24-18)10-7-4-5-8-11-20(22)23/h4,7,12-13,15-19,21H,2-3,5-6,8-11,14H2,1H3,(H,22,23)/b7-4-,13-12+/t15-,16+,17+,18-,19+/m0/s1 Y Key: YIBNHAJFJUQSRA-YNNPMVKQSA-N Y InChI=1/C20H32O5/c1-2-3-6-9-15(21)12-13-17-16(18-14-19(17)25-24-18)10-7-4-5-8-11-20(22)23/h4,7,12-13,15-19,21H,2-3,5-6,8-11,14H2,1H3,(H,22,23)/b7-4-,13-12+/t15-,16+,17+,18-,19+/m0/s1 Key: YIBNHAJFJUQSRA-YNNPMVKQBN
SMILES O=C(O)CCC/C=C\C[C@H]2[C@H]1OO[C@H](C1)[C@@H]2/C=C/[C@@H](O)CCCCC
Properties
Chemical formula	C20H32O5
Molar mass	352.465 g/mol
Density	1.129 ± 0.06 g/mL
Boiling point	490 ± 40.0 °C
Solubility in water	0.034 g/L
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

It is acted upon by:

• prostacyclin synthase to create prostacyclin
• thromboxane-A synthase to create thromboxane A2 and 12-(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (HHT) (see 12-Hydroxyheptadecatrienoic acid)
• prostaglandin D₂ synthase to create prostaglandin D₂
• prostaglandin E synthase to create prostaglandin E₂

It rearranges non-enzymatically to:

• A mixture of 12-(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (HHT) and 12-(S)-hydroxy-5Z,8Z,10E-heptadecatrienoic acid (see 12-hydroxyheptadecatrienoic acid)

Functions of prostaglandin H₂:

• regulating the constriction and dilation of blood vessels
• stimulating platelet aggregation
  • binds to thromboxane receptor on platelets' cell membranes to trigger platelet migration and adhesion to other platelets.^[5]

Effects of aspirin on prostaglandin H₂:

• Aspirin has been hypothesized to block the conversion of arachidonic acid to prostaglandin

Figure 1: Synthetic pathways from PGH₂ (the parent compound) to prostaglandins, prostacyclin and thromboxanes

References

1. Wishart, David S.; Guo, An Chi; Oler, Eponine; Wang, Fel; Anjum, Afia; Peters, Harrison; Dizon, Raynard; Sayeeda, Zinat; Tian, Siyang; Lee, Brian L.; Berjanskii, Mark; Mah, Robert; Yamamoto, Mai; Jovel Castillo, Juan; Torres Calzada, Claudia; Hiebert Giesbrecht, Mickel; Lui, Vicki W.; Varshavi, Dorna; Varshavi, Dorsa; Allen, Dana; Arndt, David; Khetarpal, Nitya; Sivakumaran, Aadhavya; Harford, Karxena; Sanford, Selena; Yee, Kristen; Cao, Xuan; Budinsky, Zachary; Liigand, Jaanus; Zhang, Lun; Zheng, Jiamin; Mandal, Rupasri; Karu, Naama; Dambrova, Maija; Schiöth, Helgi B.; Gautam, Vasuk. "Showing metabocard for Prostaglandin H2 (HMDB0001381)". Human Metabolome Database, HMDB. 5.0.
2. van der Donk WA, Tsai AL, Kulmacz RJ (December 2002). "The cyclooxygenase reaction mechanism". Biochemistry. 41 (52): 15451–8. doi:10.1021/bi026938h. PMID 12501173.
3. Salomon RG, Miller DB, Zagorski MG, Coughlin DJ (October 1984). "Prostaglandin endoperoxides. 14. Solvent-induced fragmentation of prostaglandin endoperoxides. New aldehyde products from PGH₂ and a novel intramolecular 1,2-hydride shift during endoperoxide fragmentation in aqueous solution". Journal of the American Chemical Society. 106 (20): 6049–6060. doi:10.1021/ja00332a049. ISSN 0002-7863.
4. Hla T, Neilson K (August 1992). "Human cyclooxygenase-2 cDNA". Proceedings of the National Academy of Sciences of the United States of America. 89 (16): 7384–8. Bibcode:1992PNAS...89.7384H. doi:10.1073/pnas.89.16.7384. PMC 49714. PMID 1380156.
5. Woodward DF, Jones RL, Narumiya S (September 2011). "International Union of Basic and Clinical Pharmacology. LXXXIII: classification of prostanoid receptors, updating 15 years of progress". Pharmacological Reviews. 63 (3): 471–538. doi:10.1124/pr.110.003517. PMID 21752876.