Other Electron Transport Chain Concepts - Biochemistry

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Question

A drug is introduced into cells that affects the mechanics of the electron transport chain. Specifically, this drug completely inhibits the flow of electrons through the electron transport chain and also completely halts the synthesis of ATP. Which of the following drugs is capable of doing this, and how is it accomplished?

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Answer

The correct answer is cyanide. This compound acts to inhibit cytochrome C oxidase, otherwise known as Complex IV of the electron transport chain. By inhibiting this complex, cyanide effectively halts the flow of electrons through the chain. Consequently, protons are not able to be pumped from the matrix to the intermembrane space and thus, a proton gradient cannot be established. Without a proton gradient, protons will not flow through ATP synthase, hence no ATP will be produced.

Oligomycin, on the other hand, acts to inhibit ATP synthase, which means that ATP will not be able to be produced. However, electrons are still able to flow through the chain, which means that protons are still able to be pumped across the inner membrane.

Dinitrophenol is a relatively nonpolar compound that is able to situate itself into the inner mitochondrial membrane. In doing so, it is able to dissipate the proton gradient by allowing protons to essentially be transported from the intermembrane space to the matrix without traversing through ATP synthase. Even though protons can still flow through ATP synthase to generate ATP in this scenario, the proton gradient won't be nearly as potent because they now have an alternative route to the matrix.

Methotrexate acts to competitively inhibit the enzyme known as dihydrofolate reductase. This enzyme has nothing to do with the electron transport chain, and thus will have no effect on ATP synthesis. Commonly, this drug is used as an anti-cancer agent because its substrate, dihydrofolate, is a compound that is used in the syntheis of thymine nucleotides for DNA synthesis. Inhibiting dihydrofolate reductase effectively reduces the production of thymine, which can negatively impact DNA replication in rapidly dividing cancer cells.

Likewise, allopurinol has nothing to do with the electron transport chain. This drug acts as an inhibitor of the enzyme xanthine oxidase, which is responsible for synthesizing uric acid. High levels of uric acid can lead to the development of gout, and thus, this drug is typically used to help treat people suffering from gout.

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