4.2.6 Electron Transport Chain (etc)

Introduction

The Electron Transport Chain (ETC) is the final phase of aerobic respiration. It occurs in the inner mitochondrial membrane. In this phase, the reduced coenzymes (NADH and FADH₂) produced during glycolysis, the link reaction, and the Krebs cycle are oxidized. The electrons are passed along a series of electron carriers to the final electron acceptor, molecular oxygen. The energy released during this process is used to synthesize ATP through oxidative phosphorylation.

Definition

Electron Transport Chain (ETC): The electron transport chain is a series of electron carriers located in the inner mitochondrial membrane that transfer electrons from NADH and FADH₂ to molecular oxygen, generating a proton gradient that drives ATP synthesis.

In simple words: The ETC is a chain of protein complexes that transfer electrons from NADH and FADH₂ to oxygen, producing ATP.

Core Concept

• After the Krebs cycle, most of the energy of glucose is in the form of NADH and FADH₂.
• These two molecules enter into the electron transport chain.
• In this chain, the reduced NADH and FADH₂ are oxidized.
• Their electrons are passed along a series of oxidation-reduction reactions to the final acceptor, i.e., molecular oxygen.
• Energy released during the downhill passage of electrons is used to pump protons (H⁺) from the mitochondrial matrix to the intermembrane space.
• This creates a proton gradient.
• The proton gradient activates ATP synthetase, which catalyzes ATP synthesis.
• This ATP synthesis is due to oxidation of NADH or FADH₂ in the presence of O₂, so ETC is also called oxidative phosphorylation.
• The ETC makes no ATP directly. Its function is to ease the fall of electrons from food to oxygen, releasing energy in manageable amounts.
• The mechanism that couples the ETC to ATP synthesis is called chemiosmosis.

Detailed Explanation

Location of ETC

• The ETC is located in the inner mitochondrial membrane.
• The inner membrane is folded into cristae, which increase the surface area for the ETC.
• The ETC components are embedded in the inner membrane.

Components of the Respiratory Electron Transport Chain

The components of the respiratory electron transport chain include:

Passage of Electron Flow

The passage of electrons from high-energy NADH to the first carrier and then to the next is a downhill journey with the release of energy at each step. The energy of the flowing electrons is used by some membrane carrier proteins to pump protons (H⁺) from the matrix to the intermembrane space.

Steps:

• It has two prosthetic groups: FMN and Fe-S complex.
• Both electrons and protons pass from NADH to FMN.
• FMN moves the electrons to the Fe-S complex.
• Protons are pumped to the intermembrane space.

2. FADH₂ is oxidized through ETC. - It hands over its electrons to coenzyme Q via FADH dehydrogenase complex (II).

• Complex III has three components: Cyto-b, Fe-S, and Cyto-c₁.
• This enzyme complex hands over its electron to cytochrome c.
• It also pumps protons to the intermembrane space.

4. Cytochrome c is a mobile carrier of electrons. - It delivers the electrons to cytochrome oxidase complex (IV).

5. Cytochrome oxidase complex (IV) comprises three components: Cyto-a, Cyto-a₃, and copper. - This enzyme complex acts as both an electron carrier and a proton pump.

• Oxygen is the ultimate acceptor of electrons.
• It becomes reactive.
• Each oxygen atom also picks up a pair of hydrogen ions from the aqueous solution forming water.

Equation: 12O₂ + 2H⁺ + 2e^- → H₂O

Proton Pumping Sites

Energy released during the downhill passage of electrons from one carrier to the next is used by specific transmembrane protein complexes which actively pump protons (H⁺) from the matrix to the intermembrane space. To avoid the loss of energy as unwanted heat, energy is not released in one step but in steps.

Proton pumping takes place at three specific sites of the electron transport chain by the action of three corresponding enzymes:

Electron Carriers in Detail

Science Tidbits (from textbook)

• Ubiquinone is not a protein, but a small molecule soluble in lipids and insoluble in water.
• Cytochromes literally means "cell colour".
• The reduced cytochromes are pink in colour.
• They are protein plus pigment molecules containing iron.
• They can gain or lose an electron.

ATP Yield from ETC

• Oxidation of one molecule of NADH produces 3 ATP molecules.
• Oxidation of one molecule of FADH₂ forms 2 ATP molecules.

• NADH enters the ETC at Complex I.
• FADH₂ enters the ETC at Complex II.
• NADH bypasses one proton pumping site (Site 1), so it produces less ATP.
• FADH₂ bypasses two proton pumping sites (Sites 1 and 2), so it produces even less ATP.

Chemiosmosis and Oxidative Phosphorylation

Definition: Oxidative phosphorylation is the synthesis of ATP molecules with the help of energy liberated during oxidation of reduced co-enzymes (NADH, FADH₂) produced in respiration.

• The enzyme required for this synthesis is called ATP synthetase.
• It is located in the inner mitochondrial membrane.
• It consists of two parts: F₀ and F₁.
• F₀ is embedded in the membrane and involves in the movement of protons from the intermembrane space to the mitochondrial matrix.
• F₁ (elementary particle) is a head-like part which is projected from the surface of the membrane towards the matrix.
• It catalyzes ATP synthesis by the combination of ADP and Pi.
• ATP synthetase becomes active in ATP formation only when a proton gradient having a higher concentration of H⁺ on the F₀ side as compared to the F₁ side is established.
• The flow of protons through the F₀ channel induces F₁ particles to function as ATP synthetase.
• The energy of the proton gradient is used in attaching a phosphate to ADP by a high-energy bond.
• This produces ATP.
• The theory of ATP production by this mechanism is called chemiosmosis.

Equation: ADP + Pi → ATP

Summary of ETC

Intermediate Level

Components of ETC

Electron Flow

NADH Pathway: NADH → Complex I → CoQ → Complex III → Cyto-c → Complex IV → O₂

FADH₂ Pathway: FADH₂ → Complex II → CoQ → Complex III → Cyto-c → Complex IV → O₂

Proton Pumping Sites

ATP Yield

Chemiosmosis

Important Points

• 1. After Kreb's cycle most of the energy of glucose is in the form of NADH and FADH₂.
• 2. These two molecules enter into the electron transport chain.
• 3. In this chain, the reduced NADH and FADH₂ are oxidized and their electrons are passed along a series of oxidation-reduction reaction to the final acceptor, i.e., molecular oxygen.
• 4. Components of Respiratory electron transport chain:
• - NADH-Q reductase or NADH-dehydrogenase complex (I): Further composed of FMN and Fe-S complex.
• - FADH-dehydrogenase complex (II): Contains FAD and Fe-S complex.
• - Coenzyme Q or Ubiquinone (mobile carrier): Small molecule soluble in lipids and insoluble in water.
• - Cytochrome reductase complex (III): Further composed of Cyto-b, Fe-S and Cyto-c₁.
• - Cytochrome-c (mobile carrier): Protein plus pigment molecules containing iron.
• - Cytochrome oxidase complex (IV): Further composed of Cyto-a, Cyto-a₃ and copper.
• 5. Passage of electron flow:
• - Passage of electrons from high energy NADH to first carrier to next is downhill journey with the release of energy at each step as the energy of the flowing electrons is used by some membrane carrier proteins to pump proton H⁺ from matrix to inter-membrane space.
• - Accumulation of H⁺ in the inter membrane space act as proton gradient which further activate the ATP synthetase that catalyze ATP synthesis in the presence of O₂.
• - As this ATP synthesis is due to oxidation of NADH or FADH in the presence of O₂, so ETC is also called oxidative phosphorylation.
• 6. NADH is oxidized when it reacts with NADH-dehydrogenase complex (I).
• 7. If FADH₂ is to be oxidized through ETC, it also hands over its electrons to coenzyme Q, via FADH dehydrogenase complex (II).
• 8. The flowing electrons from coenzyme Q are now transferred to cytochrome reductase complex (III) which have three components (Cyto-b, Fe-S and Cyto-c₁).
• 9. Cytochrome c delivers the electrons to cytochrome oxidase complex (IV) which comprises of three components (Cyto-a, Cyto-a₃ and copper).
• 10. Finally, the electrons are transferred to oxygen.
• 11. The oxygen is the ultimate acceptor of electrons.
• 12. Each oxygen atom also picks up a pair of hydrogen ions from the aqueous solution forming water.
• 13. Proton pumping sites:
• - Site 1: FMN → CoQ (NADH-dehydrogenase complex I)
• - Site 2: Cyto-b → Cyto-c₁ (Cytochrome reductase complex III)
• - Site 3: Cyto-a → Cyto-a₃ (Cytochrome oxidase complex IV)
• 14. Science Tidbits:
• - Ubiquinone is not a protein, but a small molecule soluble in lipids and insoluble in water.
• - Cytochromes literally means "cell colour".
• - The reduced cytochromes are pink in colour.
• - They are protein plus pigment molecules containing iron.
• - They can gain or lose an electron.
• 15. Chemiosmosis and Oxidative Phosphorylation:
• - Oxidative phosphorylation is the synthesis of ATP molecules with the help of energy liberated during oxidation of reduced co-enzymes (NADH, FADH₂) produced in respiration.
• - The enzyme required for this synthesis is called ATP synthetase.
• - It is located in the inner mitochondrial membrane.
• - It consists of two parts i.e., F₀ and F₁.
• - F₀ is embedded in the membrane and involves in the movement of protons from inter-membrane space to mitochondrial matrix.
• - F₁ or elementary particle is a head like part which is projected from the surface of membrane towards matrix.
• - It catalyzes ATP synthesis by the combination of ADP and Pi.
• - ATP-synthetase becomes active in ATP formation only when a proton gradient having higher concentration of H⁺ or protons on the F₀ side as compared to F₁ side is established.
• - The flow of protons through the F₀ channel induces F₁ particles to function as ATP-synthetase i.e., the energy of the proton gradient is used in attaching a phosphate to ADP by high energy bond.
• - This produces ATP.
• - Oxidation of one molecule of NADH₂ produces 3 ATP molecules while a similar oxidation of FADH₂ forms 2 ATP molecules.
• - The theory of ATP production by this mechanism is called chemiosmosis.

Remember

• - ETC = inner mitochondrial membrane
• - Inputs = NADH, FADH₂, O₂
• - **Outputs** = NAD⁺, FAD, H₂O, ATP
• - Final electron acceptor = oxygen
• - Proton pumping sites = 3 (Complex I, III, IV)
• - ATP yield = 1 NADH → 3 ATP; 1 FADH₂ → 2 ATP
• - **Mechanism** = chemiosmosis
• - **Enzyme** = ATP synthetase
• - Components = Complex I, II, III, IV; CoQ; Cyto-c
• - Ubiquinone = lipid-soluble mobile carrier
• - Cytochromes = iron-containing proteins

Common Mistakes

• 1. Thinking ETC occurs in the mitochondrial matrix – ETC occurs in the inner mitochondrial membrane.
• 2. Thinking oxygen is used in the Krebs cycle – Oxygen is used in the ETC.
• 3. Thinking CO₂ is produced in the ETC – CO₂ is produced in the link reaction and Krebs cycle.
• 4. Confusing the ATP yield – 1 NADH → 3 ATP; 1 FADH₂ → 2 ATP.
• 5. Thinking FADH₂ enters at Complex I – FADH₂ enters at Complex II.
• 6. Thinking NADH enters at Complex II – NADH enters at Complex I.
• 7. Forgetting the role of coenzyme Q – CoQ is a mobile carrier.
• 8. Thinking cytochrome c is a complex – Cytochrome c is a mobile carrier.
• 9. Confusing the proton pumping sites – Sites 1, 2, and 3 are at Complexes I, III, and IV.
• 10. Thinking ATP synthase is in the matrix – ATP synthase is in the inner mitochondrial membrane.
• 11. Confusing chemiosmosis with oxidative phosphorylation – Chemiosmosis is the mechanism; oxidative phosphorylation is the process.
• 12. Thinking oxygen is the final electron donor – Oxygen is the final electron acceptor.

Quick Revision

• After Kreb's cycle most of the energy of glucose is in the form of NADH and FADH₂.
• These two molecules enter into the electron transport chain.
• In this chain, the reduced NADH and FADH₂ are oxidized and their electrons are passed along a series of oxidation reduction reaction to the final acceptor i.e., molecular oxygen.
• Components of Respiratory electron transport chain include:
• Passage of electrons from high energy NADH to first carrier to next is downhill journey with the release of energy at each step as the energy of the flowing electrons is used by some membrane carrier proteins to pump proton H⁺ from matrix to inter-membrane space.
• Accumulation of H⁺ in the inter membrane space act as proton gradient which further activate the ATP synthetase that catalyze ATP synthesis in the presence of O₂.
• As this ATP synthesis is due to oxidation of NADH or FADH in the presence of O₂, so ETC is also called oxidative phosphorylation.
• NADH is oxidized when it reacts with NADH-dehydrogenase complex (I).
• It has two prosthetic groups FMN and Fe-S complex.
• Both electrons and protons pass from NADH to FMN which moves the electrons to Fe-S complex then pump the protons to intermembrane space.
• If FADH₂ is to be oxidized through ETC, it also hands over its electrons to coenzyme Q, via FADH dehydrogenase complex (II).
• The flowing electrons from coenzyme Q are now transferred to cytochrome reductase complex (III) which have three components (Cyto-b, Fe-S and Cyto-c₁).
• This enzyme complex hands over its electron to cytochrome c and also pump the electrons to intermembrane space.
• Like co-enzyme Q, cytochrome c is also mobile carrier of electrons.
• Cytochrome c delivers the electrons to cytochrome oxidase complex (IV) which comprises of three components (Cyto-a, cyto-a₃ and copper).
• This enzyme complex act as both electron carrier and proton pump.
• Finally, the electrons are transferred to oxygen.
• The oxygen is the ultimate acceptor of electrons.
• It becomes reactive.
• Each oxygen atom also picks up a pair of hydrogen ions from the aqueous solution forming water.
• Energy released during downhill passage of electrons from one carrier to the next is used to pump protons H⁺ from the mitochondrial matrix to the inter membrane space.
• Energy released during downhill passage of electrons from one carrier to next is used by specific transmembrane protein complexes which actively pump protons H⁺ from matrix to intermembrane space.
• To avoid the loss of energy as unwanted heat, energy is not released in one step rather in steps.
• Proton pumping takes place at three specific sites of electron transport chain by action of three corresponding enzymes listed below:
• Site-1: FMN → CoQ (NADH-dehydrogenase complex-I)
• Site-2: Cyto-b → cyto-c₁ (Cytochrome reductase complex-III)
• Site-3: Cyto-a → cyto-a₃ (Cytochrome complex-IV)
• The electron transport chain makes no ATP directly.
• Its function is to ease the fall of electrons from food to oxygen releasing energy in manageable amounts.
• How does the mitochondrion couple this electron transport chain and energy to ATP synthesis?
• The answer is a mechanism called chemiosmosis.
• Science Tidbits: Ubiquinone is not a protein, but a small molecule soluble in lipids and insoluble in water. Cytochromes literally means "cell colour". The reduced cytochromes are pink in colour. They are protein plus pigment molecules containing iron. They can gain or lose an electron.

60-Second Revision

• ETC = inner mitochondrial membrane
• Inputs = NADH, FADH₂, O₂
• **Outputs** = NAD⁺, FAD, H₂O, ATP
• Final electron acceptor = oxygen
• Proton pumping sites = 3 (Complex I, III, IV)
• ATP yield = 1 NADH → 3 ATP; 1 FADH₂ → 2 ATP
• **Mechanism** = chemiosmosis
• **Enzyme** = ATP synthetase
• Components = Complex I, II, III, IV; CoQ; Cyto-c
• Ubiquinone = lipid-soluble mobile carrier
• Cytochromes = iron-containing proteins
• Warning: ETC occurs in the inner mitochondrial membrane, not the matrix. Oxygen is the final electron acceptor. CO₂ is not produced in the ETC. NADH enters at Complex I; FADH₂ enters at Complex II. 1 NADH → 3 ATP; 1 FADH₂ → 2 ATP. Chemiosmosis is the mechanism of ATP synthesis. Ubiquinone and cytochrome c are mobile carriers. Cytochromes contain iron. Cyanide inhibits Complex IV.