Molecular Therapeutics

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The scientific journey of cyclooxygenase began as early as the 1930s when prostaglandins were first discovered in human semen (Bindra, 1977). Albeit, due to the relative instability and low concentration of prostaglandin found in the semen, it was difficult to clearly identify them for almost thirty years afterwards…

Introduction


Later in 1970, the mechanism of prostaglandin biosynthesis was demonstrated to involve the formation of bicyclic peroxides or endoperoxides as the initial product of polyunsaturated fatty acid oxygenation. Prostaglandin endoperoxides were successfully isolated and the name 'cyclooxygenase' came into existence as a term that describes the enzyme that is responsible for this complex biochemical transformation (Lawrence et al 1999; Hamberg and Samuelson 1973).
According to Lawrence and his colleagues (1999), the chemical process catalysed by cyclooxygenase; the conversion of arachidonic acid, (which is known to be the precursor to prostaglandins), to Prostaglandin G2 (PGG2) involves the enzymatic removal of the 13-pro-S-hydrogen, giving rise to a Pentadienyl radical with maximal electron density at C-11 and C-15. Trapping of the carbon radical at C-11 with Oxygen produces a peroxyl radical, which when added to C-9 generates a cyclic peroxide and a carbon-centred radical at C-8. The double bond at C-12 become re-inforced by the C-8 radical, generating the bicyclic peroxide and an allylic radical with maximal electron density at C-13 and C-15. The carbon radical at C-15 is trapped with oxygen to form a peroxyl radical, which is reduced to prostaglandin G2.
Cyclooxygenase came t ...
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