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. 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). 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.

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

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.

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

Effects of aspirin on prostaglandin H₂:

• 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.

References