Question

Rotenone is a toxic natural product from plants that strongly inhibits NADH dehydrogenase. Antimycin A is a toxic antibiotic that strongly inhibits the oxidation of ubiquinol.

a) Explain the mechanistic basis for the toxicity of these molecules.

b) Which of these would be a more potent poison? Explain.

Answer 1

Question (a)

Answer.

Rotenone- It inhibits the transfer of electrons from iron-sulfur centers in complex-I to ubiquinone. Therefore unused oxygen which is the terminal oxygen acceptor in the electron transport chain is reduced to radical, creating reactive oxygen species, which can damage DNA and other components of the mitochondria.

Rotenone also inhibits microtubule assembly.

Antimycin A- inhibits the flow of electrons through complex III of the ETC by blocking the passage of electrons from cytochrome b to cytochrome c.

Question (b)

Answer. Antimycin A is more potent inhibitor of ETC than Rotenone because it blocks all electron flow to oxygen while rotenone blocks electron flow from NADH, but not from FADH₂.