How do anti-inflammatory drugs work as enzyme inhibitors?

Go into a drugstore or watch ads on TV, and it becomes obvious that there are many drugs that alleviate pain. Like aspirin, many of them target the prostaglandin pathway for inflammation. John Vane’s research and later work showed that aspirin irreversibly inhibits the enzyme COX. But it turns out that there are two forms of COX, called COX-1 and COX-2, and there are several kinds of prostaglandins. COX-1 catalyzes the production of protective prostaglandins that are involved with blood clotting (which is why people take aspirin to prevent future heart attacks due to blood clots) and the integrity of the lining of the stomach. COX-2 catalyzes production of prostaglandins involved with inflammation and associated pain. Aspirin inhibits both COX-1 and COX-2. So it is not surprising that people are advised to go easy on aspirin: it may block pain, but its use can lead to stomach upsets and an inability to clot blood after a wound. Knowledge of aspirin’s limitations has led to a search for inhibitors of COX-2 only. Most of them are competitive inhibitors. How would this affect how often you need to take the drug? Look up one of these drugs and read the description of how it works.

Future directions

As details at the atomic level of the binding of enzymes to substrates are worked out, biologists use the data to try to predict which substrates might bind to which enzymes. An important consideration in binding is ΔG; the less positive this parameter, the more likely binding will occur. Factors such as ionic attractions and van der Waals forces contribute to the ΔG of binding. These factors are also important in the binding of proteins to nonsubstrate molecules, including other proteins and RNA. Indeed, it is becoming apparent that in general a protein in the cell does not exist in isolation, but is bound to something(s) else. If the protein is an enzyme, its substrate binding must be its most preferred partner. Understanding all the possible molecular interactions will result in a deeper understanding of what really goes on at the chemical level inside the cell.