Molecular Therapeutics Essay Example | Topics and Well Written Essays - 1500 words

Molecular Therapeutics - Essay workoutLater 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 offshoot 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 sharpen to a Pentadienyl radical with maximal electron stringency 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 a nd a carbon-centred radical at C-8. The double confiscate 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... Prostaglandins were shown to be involved in a wide array of physiological and pathophysiological responses such as pain, inflammation, homeostasis, order of renal function and maintenance of the mucosal integrity of the stomach wall (Remmel et al 2003), their inhibition thusly spells the anti-inflammatory drug and analgesic utility of NSAIDs and also their adverse effects, such as gastrointestinal toxicity and bleeding.However, Non-steroidal anti-inflammatory drugs happen to be the most widely used drugs in the treatment of pain and inflammation, their therapeutic effects was seen to stem from their ability to inhibit cyclooxygenase indu ced prostaglandin synthesis, which was also their major source of adverse spatial relation effects. The dilemma that ensued was how to separate the pharmacologic value of these drugs from the adverse effects.In the course of the search for a particular(prenominal) inhibitor of the negative effects of prostaglandins, which could spare the positive effects while reducing the adverse effects, it was discovered that depending on the structure of the cyclooxygenase enzyme involved in their synthesis, prostaglandins could be separated into 2 groups (Green 2001). This led to the discovery of two different cyclooxygenase isozymens encoded by two genes with different protein pattern and distribution (Remmel, 2003 Lawrence et a 1999 Ouellet, 2001) with Cyclooxygenase 1 (COX-1) constitutively expressed in most cell types, including platelets while COX-2, though not found in rosy tissues of the body, was induced in response to proinflammatory and proliferative stimuli (Ouellet et al 2001) e ssentially in response to cytokines, endotoxins, mitogens and at time growth factor (Herschman, 1996) . Available body of evidence, therefore showed that the