A pharmaceutical company has sent you samples of two new metabolic inhibitors to
ID: 10544 • Letter: A
Question
A pharmaceutical company has sent you samples of two new metabolic inhibitors to characterize as possible antibiotics. Using a preparation of isolated liver mitochondria incubated in pyruvate, oxygen, ADP and Pi, you find that inhibitor A blocks both electron transport and oxidative phosphorylation. When you add inhibitor B in addition to A, you find that electron transport is restored, but NOT oxidative phosphorylation.a. How would you classify these inhibitors in terms of mode of action on electron transport and oxidative phosphorylation?
b. Name a pair of known inhibitors that give the same result.
Please explain the answer in a detailed manner.
Explanation / Answer
There may be more than one solution to this problem. Here, I'll guide you toward one possibility. For A, think of an inhibitor that would cause a problem near the end of the pathway thus backing up the pathway so the whole pathway stops. For B, think of an inhibitor that would relieve the back up at an early point in the pathway without solving the problem near the end. To find the inhibitors described below, go to the entry for "oxidative phosphorylation" in Wikipedia, read the entries and identify the inhibitors from the "Inhibitors" section: A - This inhibitor would prevent protons from passing through ATP synthase. This would increase the proton potential in the inner membrane space. This build up of protons would back up the entire electron transport chain. Both ETC and ATP synthase are stopped. B - This inhibitor would make the inner membrane leaky to protons. Protons would flow back across, relieving the back up of the ETC. The ETC chain would work again. However, protons still would not go through ATP synthase, because inhibitor A is still blocking it. Hope that was helpful.
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