In the last post I posed the question, what would happen to a metabolic pathway if we added an inhibitory drug to the middle enzyme in a linear sequence of steps? Here is the answer.
Take a sequence of enzymes that form a linear chain. Let the pathway reach steady state, now apply a drug that will inhibit the middle enzyme, what will happen?
- The initial rate of the middle enzyme will decrease.
- Since the substrate is now consumed at a lower rate, the substrate concentration will increase.
- Since the product is now produced at a lower rate, the product concentration will decrease.
- With the product decreasing, the immediate enzyme downstream will slow down.
- With the substrate increasing, the immediate enzyme upstream will slow down due to product inhibition.
- Because the immediate enzyme upstream slows down, its substrate increases.
- Because the immediate enzyme downstream slows down, its product decreases.
- Similar changes now ripple up and downstream.
- The net effect is that all metabolites upstream increase in concentration and all metabolites downstream decrease in concentration.
- The net flux through the pathway decreases.