Systems Thinking in Systems Biology: Part 2

 May 7, 2011 8:37 am

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?

1. The initial rate of the middle enzyme will decrease.
2. Since the substrate is now consumed at a lower rate, the substrate concentration will increase.
3. Since the product is now produced at a lower rate, the product concentration will decrease.
4. With the product decreasing, the immediate enzyme downstream will slow down.
5. With the substrate increasing, the immediate enzyme upstream will slow down due to product inhibition.
6. Because the immediate enzyme upstream slows down, its substrate increases.
7. Because the immediate enzyme downstream slows down, its product decreases.
8. Similar changes now ripple up and downstream.
9. The net effect is that all metabolites upstream increase in concentration and all metabolites downstream decrease in concentration.
10. The net flux through the pathway decreases.