The COX1 and COX2 enzymes that make the prostaglandins responsible for pain and
ID: 175099 • Letter: T
Question
The COX1 and COX2 enzymes that make the prostaglandins responsible for pain and inflammation are very similar in the primary structure with 60% identical amino acids. One difference between the two enzymes is that the active site of COX2 is bordered by a Valine residue. This same position in COX2 is occupied by an isoleucine residue. Use the amino acid sheet to explain what difference this small (and otherwise conservative) substitution would have on the ability of both substrates (arachidonic acid) and drugs) to get into the active site. Which enzyme would you predict was more easily inhibited by reversible NSAIDs like ibuprofen that act by sitting in the pocket and blocking access to substrate? Which enzyme is more accessible to substrates (arachidonic acid) normally?
Explanation / Answer
Ibuprofen is an nonselective inhibitor of cox. Pain & inflammation os mediated through cox2 while cox1 inhibition leads to block formation of thromboxane cox2 is more accissible to substrate.