Subsection: Inhibitors of ETC
Case Scenario 1:
A 20-year-old woman was brought to the emergency room in an unconscious state. Upon examination, she was found to be intoxicated with cyanide poisoning.
- Explain the mechanism of action of
- Mention any two other inhibitors for the same site as
- Write the reactions of the Electron Transport Chain, mentioning its components in this
Answer:
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- a) Mechanism of Action of Cyanide:
- Cyanide inhibits cytochrome c oxidase (Complex IV) in the electron transport chain (ETC).
- It binds to the ferric ion (Fe³⁺) in cytochrome a₃, preventing the transfer of electrons to oxygen, the final electron acceptor.
- This stops ATP production via oxidative phosphorylation, leading to cellular hypoxia and energy failure, especially in vital organs like the brain and heart.
- b) Two Other Inhibitors of the Same Site (Complex IV):
- Carbon monoxide (CO)
- Hydrogen sulfide (H₂S)
Both inhibit Cytochrome C oxidase, similar to cyanide.
- c) Reactions of Electron Transport Chain (ETC) and Its Components:
The ETC occurs in the inner mitochondrial membrane and includes the following complexes:
- Complex I (NADH dehydrogenase):
NADH → NAD⁺ + H⁺ + 2e⁻ (electrons passed to CoQ) - Complex II (Succinate dehydrogenase):
FADH₂ → FAD + 2e⁻ (electrons also passed to CoQ) - Coenzyme Q (CoQ):
Transfers electrons from Complex I & II to Complex III. - Complex III (Cytochrome bc₁ complex):
Transfers electrons from CoQ to cytochrome c. - Cytochrome c:
Carries electrons to Complex IV. - Complex IV (Cytochrome c oxidase):
Transfers electrons to oxygen (O₂) → forms H₂O.
→ This step is blocked by cyanide. - ATP Synthase (Complex V):
Uses the proton gradient to synthesize ATP from ADP + Pi.
Case Scenario 2:
A 35-year-old laboratory technician is brought to the emergency department after being exposed to sodium azide while working with laboratory chemicals. He reports experiencing dizziness, headache, nausea, and shortness of breath shortly after the exposure.
- The enzyme inhibited by azide belongs to which category of enzymes of biological oxidation?
- Mention any two other inhibitors for the same site as
- Write the reactions of Electron Transport Chain mentioning its components in present
Answer:
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- a) Enzyme Inhibited by Azide:
- Azide inhibits Cytochrome c oxidase (Complex IV) in the Electron Transport Chain (ETC).
- This enzyme belongs to the oxidoreductase class of enzymes involved in biological oxidation.
- b) Two Other Inhibitors of the Same Site (Cytochrome c Oxidase):
- Cyanide (CN⁻)
- Carbon Monoxide (CO)
These agents, like azide, inhibit Complex IV, preventing electron transfer to oxygen.
- c) Reactions of Electron Transport Chain (ETC) and Its Components:
The ETC is located in the inner mitochondrial membrane and involves these steps:
- Complex I (NADH dehydrogenase):
NADH → NAD⁺ + H⁺ + 2e⁻ → electrons transferred to Coenzyme Q (CoQ) - Complex II (Succinate dehydrogenase):
FADH₂ → FAD + 2e⁻ → electrons also passed to CoQ - Coenzyme Q (Ubiquinone):
Transfers electrons from Complex I & II to Complex III - Complex III (Cytochrome bc₁ complex):
Transfers electrons to cytochrome c - Cytochrome c:
Carries electrons to Complex IV - Complex IV (Cytochrome c oxidase):
Transfers electrons to O₂, forming H₂O
→ This step is inhibited by azide in this case - ATP Synthase (Complex V):
Uses the proton gradient to generate ATP from ADP + Pi
Case Scenario 3:
A 50-year-old worker is brought to the emergency department after being exposed to hydrogen sulfide (H2S) gas while working in a confined space without adequate ventilation. He was attempting to unclog a sewer line when he suddenly collapsed. His colleagues report that he complained of a rotten egg odor before collapsing. On arrival, the patient is unresponsive and cyanotic.
- The enzyme inhibited by hydrogen sulfide (H2S) belongs to which category of enzymes of Biological oxidation?
- Describe enzymes involved in biological
Answer:
-
- a) The enzyme inhibited by hydrogen sulfide (H₂S) belongs to which category of enzymes of biological oxidation?
- Hydrogen sulfide (H₂S) inhibits Cytochrome c oxidase (Complex IV) of the Electron Transport Chain (ETC).
- This enzyme belongs to the oxidoreductase category of enzymes involved in biological oxidation.
- b) Enzymes Involved in Biological Oxidation:
Biological oxidation involves a series of enzyme systems that transfer electrons and produce ATP. The key enzyme systems are:
- Oxidases:
- Catalyze the transfer of hydrogen to oxygen (O₂) forming water or hydrogen peroxide.
- Example: Cytochrome oxidase (Complex IV of ETC)
- Dehydrogenases:
- Transfer hydrogen from one substrate to a coenzyme like NAD⁺ or FAD.
- Example: Lactate dehydrogenase, NADH dehydrogenase (Complex I)
- Hydroperoxidases:
- Break down hydrogen peroxide (H₂O₂).
- Examples: Catalase, Glutathione peroxidase
- Oxygenases:
- Incorporate oxygen directly into the substrate.
- Types:
- Monooxygenases (e.g., cytochrome P450)
- Dioxygenases (e.g., homogentisate dioxygenase)
Subsection: Uncouplers of Oxidative Phosphorylation
Case Scenario 4:
A 22-year-old medical student took part in a laboratory experiment where rats were injected with 2,4-dinitrophenol (DNP). After the injection, the rats showed increased oxygen consumption, elevated body temperature, and decreased ATP levels, despite the mitochondria being functionally intact. This reaction puzzled the student, as oxidative phosphorylation seemed to be affected without inhibition of the electron transport chain enzymes.
- What is the mechanism of action of uncouplers like DNP in oxidative phosphorylation?
- Name two physiological or synthetic uncouplers and explain their effects.
- How does the action of uncouplers differ from ETC inhibitors like cyanide?
Answer:
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- a) Mechanism of Action of Uncouplers like DNP in Oxidative Phosphorylation:
- Uncouplers like DNP disrupt the proton gradient across the inner mitochondrial membrane.
- DNP acts as a protonophore, carrying protons (H⁺) across the membrane without passing through ATP synthase.
- This uncouples electron transport from ATP synthesis:
- ETC continues, so oxygen is consumed.
- ATP is not produced efficiently, as the proton motive force is lost.
- Energy is released as heat, causing hyperthermia.
- b) Two Physiological or Synthetic Uncouplers and Their Effects:
- 2,4-Dinitrophenol (DNP) – Synthetic
- Increases oxygen consumption
- Decreases ATP production
- Raises body temperature
- Thermogenin (UCP-1) – Physiological
- Found in brown adipose tissue
- Produces heat in newborns and hibernating animals
- Helps maintain body temperature
- c) Difference Between Uncouplers and ETC Inhibitors (e.g., Cyanide):
Feature Uncouplers (e.g., DNP) ETC Inhibitors (e.g., Cyanide) Site of action Proton gradient (membrane) Specific ETC enzymes (e.g., Complex IV) ETC activity Continues Stops completely Oxygen consumption Increased Decreased or stopped ATP synthesis Decreased Decreased Heat production Increased Not increased
Case Scenario 5:
A newborn baby was placed in a cool environment shortly after birth. Despite the drop in external temperature, the baby maintained a relatively stable core body temperature without shivering. A pediatrician explained that this is due to the presence of brown adipose tissue (BAT) and a protein called thermogenin (UCP-1) that plays a key role in non-shivering thermogenesis.
- What is thermogenin, and where is it found in the body?
- Explain the mechanism by which thermogenin acts as a physiological uncoupler of oxidative phosphorylation.
- Why is this mechanism important in newborns and certain animals? (2 marks)
Answer:
- Thermogenin, also known as uncoupling protein-1 (UCP-1), is a specialized protein located in the inner mitochondrial membrane of brown adipose tissue (BAT).
- Thermogenin (UCP-1) creates an alternative channel for protons to flow back into the matrix without generating ATP. This “uncouples” the proton gradient from ATP synthesis. Instead of producing ATP, the energy is released as heat, a process known as non-shivering thermogenesis. This allows the body to maintain temperature without muscle activity or ATP production.
- Newborns have a limited ability to shiver, so non-shivering thermogenesis via thermogenin is essential to maintain body temperature in cold environments. Similarly, hibernating animals use thermogenin in brown fat to generate heat during arousal from hibernation. This mechanism ensures survival in cold climates and helps regulate body temperature.