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.

[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.