Chemistry:Prostaglandin H2

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Prostaglandin H2[1]
Names
Other names
PGH2, Endoperoxide H2, Prostaglandin R2
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
MeSH Prostaglandin+H2
UNII
Properties
C20H32O5
Molar mass 352.465 g/mol
Density 1.129 ± 0.06 g/mL
Boiling point 490 ± 40.0 °C
0.034 g/L
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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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:

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[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. ↑ 1.0 1.1 Wishart, David S.; Djombou Feunang, Yannick; Marcu, Ana; Guo, An Chi; Liang, Kevin; Vázquez Fresno, Rosa; Sajed, Tanvir; Johnson, Daniel et al.. "Showing metabocard for Prostaglandin H2 (HMDB0001381)". http://www.hmdb.ca/metabolites/HMDB0001381. 
  2. ↑ "The cyclooxygenase reaction mechanism". Biochemistry 41 (52): 15451–8. December 2002. doi:10.1021/bi026938h. PMID 12501173. 
  3. ↑ Salomon, Robert G.; Miller, Donald B.; Zagorski, Michael G.; Coughlin, Daniel J. (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. ↑ "Human cyclooxygenase-2 cDNA". Proceedings of the National Academy of Sciences of the United States of America 89 (16): 7384–8. August 1992. doi:10.1073/pnas.89.16.7384. PMID 1380156. Bibcode: 1992PNAS...89.7384H. 
  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. https://www.sciencedirect.com/science/article/pii/S0049017206000497. 
  6. ↑ Hirata, Takako; Narumiya, Shuh (2011-08-05). "Prostanoid Receptors" (in EN). doi:10.1021/cr200010h. https://pubs.acs.org/doi/pdf/10.1021/cr200010h. 
  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" (in en). Journal of Neurochemistry 82 (4): 1003–1006. doi:10.1046/j.1471-4159.2002.01064.x. ISSN 1471-4159. https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1471-4159.2002.01064.x. 
  8. ↑ "International Union of Basic and Clinical Pharmacology. LXXXIII: classification of prostanoid receptors, updating 15 years of progress". Pharmacological Reviews 63 (3): 471–538. September 2011. doi:10.1124/pr.110.003517. PMID 21752876. 
  9. ↑ 9.0 9.1 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. https://www.sciencedirect.com/science/article/pii/0005276073901458. 
  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. https://www.sciencedirect.com/science/article/pii/0003269786905099. 



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