Prostaglandin H2

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

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. PGH₂ is produced by every type of cell except for red blood cells and has a wide range of effects in the body. ^[5]

Eicosanoid synthesis – prostaglandin H₂ near center

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
• prostaglandin F synthase to create prostaglandin F_2α ^[6]

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)
  • These breakdown products are associated with increased aggregation of Amyloid beta peptides and Alzheimer's disease. ^[7]

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 ^[8]

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

History

Prostaglandin H₂ was discovered in 1973 by Diederik H. Nugteren and Elly Christ-Hazelhof while they were researching the formation of prostaglandin E₂ from arachidonic acid using enzymes found in vesicular glands. ^[9]

Synthesis

The original synthesis of prostaglandin H₂ by Diederik H. Nugteren and Elly Christ-Hazelhof was performed in 1973. ^[9] Sheep vesicular glands were homogenized with 1M KH₂PO₄ and 0.001 M EDTA buffer and then centrifuged to isolate the COX-1 enzymes. Pure arachidonic acid was added to a solution containing the enzymes, and the mixture was shaken. Thin-layer chromatography was used to isolate a band of prostaglandin H₂.

In 1986, due to low prostaglandin H₂ product purity from thin-layer chromatography and column chromatography, high-performance liquid chromatography with hexane and isopropanol as solvents was developed as an alternative means of isolating the prostaglandin with 98% purity. ^[10]

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. Miller, Stephen B. (2006-08-01). "Prostaglandins in Health and Disease: An Overview". Seminars in Arthritis and Rheumatism. 36 (1): 37–49. doi:10.1016/j.semarthrit.2006.03.005. ISSN   0049-0172.
6. Hirata, Takako; Narumiya, Shuh (2011-08-05). "Prostanoid Receptors". ACS Publications. doi:10.1021/cr200010h . Retrieved 2025-11-16.
7. Boutaud, Olivier; Ou, Joyce J.; Chaurand, Pierre; Caprioli, Richard M.; Montine, Thomas J.; Oates, John A. (2002). "Prostaglandin H2 (PGH2) accelerates formation of amyloid β1−42 oligomers". Journal of Neurochemistry. 82 (4): 1003–1006. doi:10.1046/j.1471-4159.2002.01064.x. ISSN   1471-4159.
8. 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.
9. Nugteren, D. H.; Hazelhof, E. (1973-12-20). "Isolation and properties of intermediates in prostaglandin biosynthesis". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 326 (3): 448–461. doi:10.1016/0005-2760(73)90145-8. ISSN   0005-2760.
10. Zulak, I. M.; Puttemans, M. L.; Schilling, A. B.; Hall, E. R.; Venton, D. L. (1986-04-01). "A fast, nondestructive purification scheme for prostaglandin H2 using a nonaqueous, bonded-phase high-performance liquid chromatography system". Analytical Biochemistry. 154 (1): 152–161. doi:10.1016/0003-2697(86)90509-9. ISSN   0003-2697.