Question

Effect of Rotenone and Antimycin A on Electron Transfer 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. a. Explain why rotenone ingestion is lethal to some insect and fish species. b. Explain why antimycin A is a poison. c. Given that rotenone and antimycin A are equally effective in blocking their respective sites in the electron-transfer chain, which would be a more potent poison? Explain.

Short answer

Rotenone and Antimycin A block ATP production. Antimycin A is more potent as it inhibits a central ETC component, affecting more reactions and resulting in energy collapse.

Step-by-step solution

Understanding Rotenone's Effect

Rotenone inhibits NADH dehydrogenase, also known as complex I. This enzyme is responsible for transferring electrons from NADH to the electron transport chain (ETC). When rotenone blocks complex I, it prevents the flow of electrons into the ETC, reducing ATP production. The lack of ATP, an essential energy source, leads to cell death, especially in organisms heavily reliant on aerobic respiration such as insects and fish.

Analyzing Antimycin A's Mechanism

Antimycin A inhibits cytochrome bc1 complex, also known as complex III, which is responsible for the transfer of electrons from ubiquinol to cytochrome c in the ETC. By blocking complex III, Antimycin A disrupts electron flow, halting ATP production in the same way as rotenone but at a different stage in the chain. This also leads to energy depletion and cell death.

Comparing Potency of Rotenone and Antimycin A

Both rotenone and antimycin A stop ATP production by blocking the electron transport chain; however, their site of action is different. Rotenone acts at the beginning of the chain (complex I), while Antimycin A acts further along (complex III). When the ETC is blocked by antimycin A, electrons cannot pass beyond complex III, resulting in more profound effects throughout entire cellular systems. Thus, antimycin A would theoretically be more potent because it not only stops the electron flow but also halts the subsequent reactions earlier than complex I inhibition does.

Key concepts

NADH Dehydrogenase

NADH Dehydrogenase, also referred to as Complex I, plays a crucial role in cellular respiration. It serves as the first enzyme in the electron transport chain (ETC), which is located in the inner membrane of mitochondria. Its primary function is to accept electrons from NADH, a product of metabolic processes such as glycolysis and the Krebs cycle. NADH Dehydrogenase transfers these electrons to ubiquinone, which is a carrier molecule in the ETC.

• This process is vital for creating a proton gradient across the mitochondrial membrane.
• The gradient is used to produce ATP, the energy currency of cells.

The interruption of this electron transfer process by inhibitors like rotenone halts ATP production, illustrating the enzyme's indispensable role in energy metabolism.

Complex I Inhibition

Complex I Inhibition occurs when substances like rotenone bind to NADH dehydrogenase, preventing it from accepting electrons from NADH. This blockage disrupts the normal electron flow into the electron transport chain.

• The electrons are unable to be passed down the chain.
• Without electron flow, no proton gradient can be established.
• Consequently, ATP synthesis is significantly reduced.

The reduction in ATP synthesis can be detrimental, especially to organisms reliant on a high ATP turnover for survival, leading to cell death. This type of inhibition is why rotenone can be lethal when ingested by insects and fish.

Complex III Inhibition

Complex III, also known as cytochrome bc1 complex, facilitates the transfer of electrons from ubiquinol to cytochrome c. Antimycin A is known to inhibit this complex by preventing electron movement at this crucial juncture.

• By blocking electron flow, Antimycin A brings ATP production to a halt.
• This cessation impacts cellular respiration significantly beyond just blocking a single step as it affects all downstream components.
• Energy-starved cells result in physiological failure and ultimately, organismal death.

Because Complex III is situated further down the electron transport chain than Complex I, inhibition at this site may have more widespread effects on a cell's metabolism.

ATP Production

ATP Production is the primary purpose of the electron transport chain. ATP acts as the main energy currency in biological systems, providing the necessary power for countless cellular processes.
The electron transport chain contributes to ATP production by establishing a proton gradient across the mitochondrial membrane, driven by the sequential transfer of electrons through various complexes and carriers.

• This proton gradient drives ATP synthesis through ATP synthase.
• When inhibitors like rotenone or antimycin A disrupt this process, ATP cannot be generated.
• A scarcity of ATP means critical cellular functions cannot be sustained, leading to cell death.

Thus, maintaining an uninterrupted electron flow through the chain is critical for sustaining life.

Cellular Respiration

Cellular Respiration encompasses the entire process by which cells convert nutrients into energy in the form of ATP. This multi-step process includes glycolysis, the Krebs cycle, and the electron transport chain.
The electron transport chain, a key component, is the final stage of cellular respiration and is where most ATP is produced.

• Electron donors like NADH and FADH2 feed electrons into the chain.
• The energy released is used to pump protons across the inner mitochondrial membrane.
• The return flow of these protons through ATP synthase leads to ATP creation.

Inhibitors that target electron transport chain components, such as rotenone and antimycin A, thwart this essential ATP-producing process, demonstrating the intricate link between cellular respiration and organismal energy homeostasis.

Metabolic Poisons

Metabolic Poisons are substances that disrupt key metabolic pathways in organisms. They can inhibit vital processes like the electron transport chain, leading to a severe impact on cellular energy production.

• Rotenone and antimycin A serve as classic examples of metabolic poisons.
• Both inhibit distinct complexes within the electron transport chain but effectively stop ATP production.
• The consequences of using such poisons include energy depletion, cessation of cellular functions, and organism death.

Understanding how these poisons operate offers insight into the delicate balance of cellular metabolic processes necessary for life, highlighting the vast impacts disruptions can have at even seemingly minor points within a cellular pathway.