Prostaglandin H
2 is a type of
prostaglandin
The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are deriv ...
and a precursor for many other biologically significant molecules. It is synthesized from
arachidonic acid
Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''ara ...
in a reaction catalyzed by a
cyclooxygenase
Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, ) that is responsible for formation of prostanoids, including thromboxane and prostaglandins such as pr ...
enzyme. The conversion from
Arachidonic acid
Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''ara ...
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
Prostaglandin G2 is an organic peroxide belonging to the family of prostaglandins. The compound has been isolated as a solid, although it is usually used in vivo. It quickly converts into prostaglandin H2, a process catalyzed by the enzyme COX. ...
. Second,
COX-2 reduces the peroxide functional group to a
Secondary alcohol
In chemistry, an alcohol is a type of organic compound that carries at least one hydroxyl () functional group bound to a saturated carbon atom. The term ''alcohol'' originally referred to the primary alcohol ethanol (ethyl alcohol), which is ...
, forming Prostaglandin H2. Other peroxidases like
Hydroquinone
Hydroquinone, also known as benzene-1,4-diol or quinol, is an aromatic organic compound that is a type of phenol, a derivative of benzene, having the chemical formula C6H4(OH)2. It has two hydroxyl groups bonded to a benzene ring in a ''pa ...
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.
It is acted upon by:
*
Prostacyclin synthase
Prostaglandin-I synthase () also known as prostaglandin I2 (prostacyclin) synthase (PTGIS) or CYP8A1 is an enzyme involved in prostanoid biosynthesis that in humans is encoded by the ''PTGIS'' gene. This enzyme belongs to the family of cytochrome ...
to create
prostacyclin
Prostacyclin (also called prostaglandin I2 or PGI2) is a prostaglandin member of the eicosanoid family of lipid molecules. It inhibits platelet activation and is also an effective vasodilator.
When used as a drug, it is also known as epoprosten ...
*
Thromboxane-A synthase to create
thromboxane A2
Thromboxane A2 (TXA2) is a type of thromboxane that is produced by activated platelets during hemostasis and has prothrombotic properties: it stimulates activation of new platelets as well as increases platelet aggregation. This is achieved by ac ...
and 12-(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (HHT) (see
12-Hydroxyheptadecatrienoic acid)
*
Prostaglandin D2 synthase
Prostaglandin-H2 D-isomerase (PTGDS) is an enzyme that in humans is encoded by the ''PTGDS'' gene.
Function
The protein encoded by this gene is a glutathione-independent prostaglandin D synthase that catalyzes the conversion of prostaglandin ...
to create
prostaglandin D2
Prostaglandin D2 (or PGD2) is a prostaglandin that binds to the receptor PTGDR (DP1), as well as CRTH2 (DP2). It is a major prostaglandin produced by mast cells – recruits Th2 cells, eosinophils, and basophils. In mammalian organs, large a ...
*
Prostaglandin E synthase
Prostaglandin E synthase (, or PGE synthase) is an enzyme involved in eicosanoid and glutathione metabolism, a member of MAPEG family. It generates prostaglandin E (PGE) from prostaglandin H2.
The synthase generating PGE2 is a membrane-associat ...
to create
prostaglandin E2
Prostaglandin E2 (PGE2), also known as dinoprostone, is a naturally occurring prostaglandin with oxytocic properties that is used as a medication. Dinoprostone is used in labor induction, bleeding after delivery, termination of pregnancy, and ...
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)
Use of prostaglandin H
2:
* 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 H
2:
* Aspirin has been hypothesized to block the conversion of arachidonic acid to prostaglandin
References
Organic peroxides
Prostaglandins
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