Prostaglandin H2 Explained

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.^[1] 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).^[2] 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.^[3] PGH2 is unstable at room temperature, with a half life of 90-100 seconds,^[4] so it is often converted into a different prostaglandin.

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

Notes and References

1. van der Donk WA, Tsai AL, Kulmacz RJ . The cyclooxygenase reaction mechanism . Biochemistry . 41 . 52 . 15451–8 . December 2002 . 12501173 . 10.1021/bi026938h .
2. Salomon. Robert G.. Miller. Donald B.. Zagorski. Michael G.. Coughlin. Daniel J. . vanc . 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. 10.1021/ja00332a049. 0002-7863.
3. Hla T, Neilson K . Human cyclooxygenase-2 cDNA . Proceedings of the National Academy of Sciences of the United States of America . 89 . 16 . 7384–8 . August 1992 . 1380156 . 49714 . 10.1073/pnas.89.16.7384 . 1992PNAS...89.7384H . free .
4. David S. Wishart. Showing metabocard for Prostaglandin H2 (HMDB0001381).
5. Woodward DF, Jones RL, Narumiya S . 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 . 21752876 . 10.1124/pr.110.003517 . free .