Introduction to Electron Transport Chain (ETC):
The Electron Transport Chain (ETC), also called the Respiratory Chain, represents the final stage of the oxidation of carbohydrates, fats, and amino acids. These nutrients are metabolized to produce NADH and FADH₂, which act as carriers of electrons (reducing equivalents).
The ETC transfers these electrons through a series of oxidation–reduction reactions to oxygen (O₂), the final electron acceptor. This process releases energy, which is captured in the form of ATP by a process called oxidative phosphorylation.
Localization of the Electron Transport Chain
The electron transport chain is located in the inner mitochondrial membrane. Its enzymes and electron carriers are embedded in this membrane, while protons are pumped into the intermembrane space, creating an electrochemical gradient essential for ATP synthesis.
Components of the Electron Transport Chain
The ETC consists of several key components that function as electron carriers and redox centers:
- Nicotinamide adenine dinucleotide (NAD⁺)
- Flavin mononucleotide (FMN) and Flavin adenine dinucleotide (FAD)
- Coenzyme Q (Ubiquinone)
- Iron-sulfur (Fe-S) proteins
- Cytochromes — b, c₁, c, a, and a₃
Among these, cytochrome c is water-soluble and mobile, while the others are fixed in the membrane. Cytochrome a₃ (also known as cytochrome oxidase) contains copper ions essential for oxygen reduction.
Coenzyme Q is a fat-soluble quinone compound that moves freely within the lipid bilayer of the inner membrane, transferring electrons between complexes.
Structural Organization of the Electron Transport Chain
The ETC is organized into four enzyme complexes (Complex I to IV), each responsible for specific redox reactions:
- Complex I — NADH-CoQ Reductase: Transfers electrons from NADH to Coenzyme Q.
- Complex II — Succinate-CoQ Reductase: Transfers electrons from succinate (via FADH₂) to Coenzyme Q.
- Complex III — CoQ-Cytochrome c Reductase: Transfers electrons from CoQH₂ to Cytochrome c.
- Complex IV — Cytochrome Oxidase: Transfers electrons from Cytochrome c to oxygen, forming water.
These complexes are arranged in order of increasing redox potential, allowing electrons to flow from carriers with lower potential (like NADH) to those with higher potential (like oxygen).
Reactions of the Electron Transport Chain
Step-by-Step Sequence:
- Formation of NADH: Dehydrogenases oxidize substrates (MH₂), transferring two hydrogen atoms to NAD⁺, forming NADH + H⁺.
- Transfer to FMN: NADH donates two electrons and one proton to FMN (flavin mononucleotide) within Complex I, forming FMNH₂.
- Iron-Sulfur Proteins: The electrons from FMNH₂ are passed to Fe-S proteins, which transfer only electrons (not protons).
- Reduction of Coenzyme Q: CoQ accepts two electrons from Fe-S proteins and two protons from the matrix, becoming CoQH₂. It also receives electrons from FADH₂ in Complex II.
- Cytochrome Chain: CoQH₂ transfers electrons to cytochrome b → c₁ → c → a → a₃, releasing protons into the intermembrane space.
- Final Step: Cytochrome oxidase (cytochrome a₃) transfers electrons to oxygen, which combines with protons to form water.
Reaction Summary:
NADH + H⁺ + ½ O₂ → NAD⁺ + H₂O + Energy (ATP)
Formation of ATP
The energy released during electron transfer is used to synthesize ATP from ADP and inorganic phosphate (Pi) by the enzyme ATP synthase (F₀F₁-ATPase). This coupling of oxidation with phosphorylation is known as oxidative phosphorylation.
Sites of ATP Synthesis:
There are three major sites in the ETC where ATP is synthesized:
- Oxidation of FMNH₂ by CoQ (Complex I)
- Oxidation of Cytochrome b by Cytochrome c₁ (Complex III)
- Cytochrome oxidase reaction (Complex IV)
ATP Yield:
- Electrons from NADH pass through all three sites → yield 3 ATP.
- Electrons from FADH₂ enter at Complex II, bypassing the first site → yield 2 ATP.
Inhibitors of the Electron Transport Chain
ETC inhibitors are divided into three categories:
1. Inhibitors of the Electron Transport Chain Proper
These agents block electron flow through specific complexes:
| Complex | Inhibitors | Effect |
|---|---|---|
| Complex I (NADH → CoQ) | Rotenone, Amobarbital, Piericidin A | Block electron transfer from Fe-S proteins to CoQ |
| Complex III (Cyt b → Cyt c₁) | Antimycin A, Dimercaprol, BAL | Inhibit electron transfer between cytochromes |
| Complex IV (Cyt a₃ → O₂) | Cyanide, Carbon monoxide, Hydrogen sulfide (H₂S) | Prevent oxygen reduction, halting respiration |
2. Inhibitors of Oxidative Phosphorylation (ATP Synthase Inhibitors)
These substances block ATP synthesis by directly inhibiting ATP synthase (F₀F₁-ATPase) without affecting electron transport.
- Example: Oligomycin — an antibiotic that completely blocks phosphorylation.
3. Uncouplers of Oxidative Phosphorylation
Uncouplers allow electron transport to continue but prevent ATP synthesis by disrupting the proton gradient across the inner mitochondrial membrane. The energy is released as heat instead of ATP.
They are typically lipid-soluble and transport protons across the membrane, dissipating the electrochemical gradient.
- Examples: 2,4-Dinitrophenol (DNP), Dicumoral, Salicylate (aspirin metabolite)
Physiological Uncouplers:
- Thermogenin — found in brown adipose tissue; produces heat during non-shivering thermogenesis.
- Thyroxine, Bilirubin, and Free Fatty Acids — may act as weak uncouplers under certain conditions.
Ionophores
Ionophores are lipid-soluble compounds that transport specific cations across the mitochondrial membrane. They disrupt the electrochemical gradient required for ATP synthesis, thereby inhibiting oxidative phosphorylation.
- Examples: Valinomycin and Gramicidin
Summary of the Electron Transport Chain
| Complex | Main Components | Electron Donor | Electron Acceptor |
|---|---|---|---|
| I | NADH dehydrogenase, FMN, Fe-S proteins | NADH | Coenzyme Q |
| II | Succinate dehydrogenase, FAD, Fe-S proteins | FADH₂ | Coenzyme Q |
| III | Cytochromes b, c₁ | CoQH₂ | Cytochrome c |
| IV | Cytochromes a, a₃ (cytochrome oxidase) | Cytochrome c | Oxygen (forms H₂O) |
Detailed Notes:
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