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Do cyclooxygenases possess a murzyme activity?

Daniel Andrew Gideon, Abhinav Parashar, Jefri Robin, Pushparaj Annadurai, Vijay Nirusimhan, Kelath Murali Manoj

Abstract

Cyclooxygenases-1 and 2 (COX1/COX2) are the key enzyme isoforms that are involved in the catalytic conversion of arachidonic acid (and other fatty acids or their intermediates) to form eicosanoid compounds. Due to their phenomenal roles in inflammation, cancer and pathophysiology of diseases (as well as in normal physiological functions), COX enzymes are some of the most well-studied enzymes and are prime pharmacological targets for blocking inflammation and pain. The longstanding classical mechanism of COX action involves the orchestrated action of two distinct activities of the enzyme - the cyclooxygenase activity and the peroxidase activity. Cyclooxygenases 1 and 2 have many similarities and differences in their substrate and inhibitor binding preferences. Although non-steroidal anti-inflammatory drugs (NSAIDs) have been used for a long time, the mechanism of COX action remains obscure. Murzymes were classically identified/elucidated in heme-cofactor containing proteins, and are defined as redox enzymes that work via diffusible reactive species (DRS). Herein, we investigate if the currently prevailing peroxidase-cyclooxygenase mechanism of COX enzyme action stands to be re-interpreted in the light of murburn concept. That is, it remains to be probed if COX enzymes present intricate equilibriums of DRS interacting with other non-specific agents in cellular/membrane milieu.

Keywords

cyclooxygenase, peroxidase, arachidonic acid, prostaglandin, inflammation, NSAIDs, murzyme, murburn concept

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DOI: http://dx.doi.org/10.14748/bmr.v32.8503

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About The Authors

Daniel Andrew Gideon
The Science & Ethics Foundation, Kulappully, Shoranur-2, Palakkad District, Kerala, India
India

Abhinav Parashar
The Science & Ethics Foundation, Kulappully, Shoranur-2, Palakkad District, Kerala, India
India

Jefri Robin
The Science & Ethics Foundation, Kulappully, Shoranur-2, Palakkad District, Kerala, India
India

Pushparaj Annadurai
The Science & Ethics Foundation, Kulappully, Shoranur-2, Palakkad District, Kerala, India
India

Vijay Nirusimhan
The Science & Ethics Foundation, Kulappully, Shoranur-2, Palakkad District, Kerala, India
India

Kelath Murali Manoj
The Science & Ethics Foundation, Kulappully, Shoranur-2, Palakkad District, Kerala, India
India

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