Prostaglandin H2
Prostaglandin H2, or prostaglandin H2, 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. 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. 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. PGH2 is unstable at room temperature, with a half life of 90–100 seconds, 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.
Image:Eicosanoid synthesis.svg|thumb|left|320px|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--hydroxy-5Z,8E,10E-heptadecatrienoic acid
- prostaglandin D2 synthase to create prostaglandin D2
- prostaglandin E synthase to create prostaglandin E2
- prostaglandin F synthase to create prostaglandin F2α
- A mixture of 12--hydroxy-5Z,8E,10E-heptadecatrienoic acid and 12--hydroxy-5Z,8Z,10E-heptadecatrienoic acid
- * These breakdown products are associated with increased aggregation of Amyloid beta peptides and Alzheimer's disease.
- 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
- Aspirin has been hypothesized to block the conversion of arachidonic acid to prostaglandin
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.Synthesis
The original synthesis of prostaglandin H2 by Diederik H. Nugteren and Elly Christ-Hazelhof was performed in 1973. 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.