Rotenone, a toxic natural product from plants, strongly inhibits NADH dehydrogen
ID: 58748 • Letter: R
Question
Rotenone, a toxic natural product from plants, strongly inhibits NADH dehydrogenase of insect and fish mitochondria. Antimycin A, a toxic antibiotic, strongly inhibits the oxidation of ubiquinol (QH2).
a) Explain why rotenone ingestion is lethal.
b) Identify where in the electron transport chain antimycin A exhibits its action, and explain why it is a poison.
c) Given that both these compounds are equally effective at blocking their respective sites in the electron transport chain, which is the more potent poison? Explain fully.
Explanation / Answer
1.NADH dehydrogenase or NADH co enzyme Q reductase in mitochondria is a respiratory enzyme complex involving in oxidation .and reduction reactions. The enzyme is a flavoprotein containing FMN as prosthetic group. FMN accepts two electrons and protons to form FMNH2. In the reactions, the complex accepts electrons from NADH, involve in electron transport chain thereby producing ATP. Rotenone inhibition of NADH dehydrogenase causes decrease in the rate of flow of electrons preventing the electrochemical potential difference which further decrease the ATP production. If sufficient amount of ATP is not supplied for the cellular functions in fish and insects for long period, the organism dies. So ingestion of Rotenone is lethal.
NADH + H++ FMN ------------------> NAD++ FMNH2
2. Actimycin A inhibits electron transfer from Cytochrome b to Cytochrome c1 involving FeS in complex III causing accumulation of QH2 (ubiquinol, reduced form of ubiquinone). In absence of oxidised Ubiquinone inhibits the electron transport chain, thereby inhibiting ATP formation.
The QH2 is further reduced to semiquinone Q2-, a super radicle causing damage to lipids, nucleic acids and proteins.
Substrate------>NAD+-----> FMN---X--> CO Q( Ubiquinone)-----> Cyt b---Y---> Cyt c1-----> Cyt c----> Cyt a-----> Cyt a3---> O2
X: Rotenone Y: Actimycin
3. Rotenone inhibits electron transport only at complex I through electrons from NADH and complex II through succinate and fatty acyl Co A, whereas Antimycin A inhibits oxidation of QH2 and electron flow from all the complexe I, II, III inhibiting electron transport chain and ATP production. So Antimycin A is more potent poison.
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