4.2.3 Mechanism of Aerobic Respiration

Introduction

Aerobic respiration is the complete oxidative breakdown of organic food (especially glucose) into carbon dioxide and water with the release of a great deal of energy in the form of ATPs. It is the predominant respiratory pathway in most organisms and requires oxygen. Aerobic respiration is completed in four phases: glycolysis, oxidation of pyruvates, Krebs cycle, and respiratory electron transport chain.

Definition

Aerobic Respiration: Aerobic respiration is a catabolic process which involves the complete oxidative breakdown of organic food (especially glucose) into carbon dioxide and water with release of great deal of energy in the form of ATPs.

In simple words: Aerobic respiration is the complete breakdown of glucose using oxygen to produce carbon dioxide, water, and a large amount of energy (ATP).

Core Concept

• It is the predominant respiratory pathway in most organisms.
• It requires oxygen.
• It involves the complete oxidative breakdown of organic food.
• The final products are carbon dioxide and water.
• A great deal of energy is released in the form of ATPs.
• Aerobic respiration is completed in four phases:

Detailed Explanation

Overview of Aerobic Respiration

C₆H₁₂O₆ + 6O₂ → 6CO₂ + 6H₂O + Energy (36–38 ATP)

Phases:

Phase 1: Glycolysis

Definition: Glycolysis is the process of breakdown of glucose or similar hexose sugar into two molecules of pyruvates through a series of enzymatic reactions releasing some energy (as ATP) and reduced coenzymes (as NADH).

• Occurs in the cytoplasm.
• It is completed in two phases:
• Preparatory phase is an investment phase in which two ATPs are consumed.
• Its end products are two molecules of G3P.
• Oxidative phase is the pay-off phase in which:
• ATPs are produced through substrate-level phosphorylation.
• NADH is produced, which upon further oxidation in the respiratory electron transport chain yields more ATPs.

Steps of Glycolysis:

Net Result of Glycolysis: Glucose → 2 Pyruvate + 2 ATP + 2 NADH

• Glycolysis occurs in the cytoplasm.
• It does not require oxygen.
• It produces 2 ATP (net) and 2 NADH.
• The end product is pyruvate.

Phase 2: Oxidation of Pyruvate to Acetyl-CoA

Definition: Pyruvates are produced in cytosol. Because pyruvate is a charged molecule, it must enter the mitochondrion via active transport with the help of the transport protein pyruvate translocase.

• Pyruvate is produced in the cytosol.
• Pyruvate is a charged molecule.
• It enters the mitochondrion via active transport with the help of pyruvate translocase.
• On entering the mitochondria, pyruvates do not directly participate in Krebs cycle but they undergo an intermediate phase called oxidation of pyruvate or link reaction.
• It links the pathway of aerobic respiration that occurs outside the mitochondria with that which occurs inside the mitochondria.
• The oxidation of pyruvate takes place in three steps:
• This oxidation, decarboxylation, and addition of coenzyme A is catalyzed by a complex of three enzymes called pyruvate dehydrogenase complex.

Equation: 2 Pyruvate + 2 CoA + 2 NAD⁺ → 2 Acetyl-CoA + 2 CO₂ + 2 NADH + 2 H⁺

Phase 3: Krebs Cycle

Definition: This cycle was discovered by British scientist Sir Hans Krebs, therefore, called Krebs cycle. It is also called Citric acid cycle or Tri carboxylic acid (TCA) cycle because the first product is citric acid.

• Occurs in the mitochondrial matrix.
• Also called Citric acid cycle or TCA cycle.
• The first product is citric acid (6C).
• Acetyl-CoA (2C) combines with oxaloacetate (4C) to form citrate (6C).

Steps of Krebs Cycle:

Net Result of Krebs Cycle (per acetyl-CoA): 3 NADH + 1 FADH₂ + 1 GTP + 2 CO₂

Net Result of Krebs Cycle (per glucose): 6 NADH + 2 FADH₂ + 2 ATP + 4 CO₂

• Krebs cycle occurs in the mitochondrial matrix.
• It produces NADH, FADH₂, ATP, and CO₂.
• The cycle is named after Sir Hans Krebs.
• It is also called the citric acid cycle or TCA cycle.

Phase 4: Electron Transport Chain (ETC)

Definition: After 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 and their electrons are passed along a series of oxidation-reduction reactions to the final acceptor, i.e., molecular oxygen.

• Occurs in the inner mitochondrial membrane.
• NADH and FADH₂ are oxidized.
• Electrons are passed along a series of carriers.
• The final electron acceptor is molecular oxygen.
• Energy is used to pump protons (H⁺) from the matrix to the intermembrane space.
• The proton gradient drives ATP synthesis by ATP synthase.
• This process is called oxidative phosphorylation.

Components of ETC:

• NADH is oxidized by NADH dehydrogenase complex (I).
• Electrons pass to coenzyme Q.
• FADH₂ is oxidized by FADH dehydrogenase complex (II).
• Electrons pass to coenzyme Q.
• Coenzyme Q passes electrons to cytochrome reductase complex (III).
• Cytochrome reductase passes electrons to cytochrome c.
• Cytochrome c passes electrons to cytochrome oxidase complex (IV).
• Cytochrome oxidase passes electrons to oxygen.
• Oxygen accepts electrons and forms water.

Proton Pumping Sites:

• 1 NADH → 3 ATP
• 1 FADH₂ → 2 ATP

• Glycolysis: 2 ATP + 2 NADH → 2 + 6 = 8 ATP (or 4 ATP in eukaryotes due to NADH transport)
• Oxidation of pyruvate: 2 NADH → 6 ATP
• Krebs cycle: 6 NADH + 2 FADH₂ + 2 ATP → 18 + 4 + 2 = 24 ATP
• Total: 36–38 ATP

Equation: NADH + H⁺ + 12O₂ → NAD⁺ + H₂O + Energy

Summary of Aerobic Respiration

Intermediate Level

Glycolysis in Detail

Oxidation of Pyruvate in Detail

Krebs Cycle in Detail

Electron Transport Chain in Detail

Summary of ATP Yield

Important Points

• 1. Aerobic respiration is a catabolic process which involves the complete oxidative breakdown of organic food (especially glucose) into carbon dioxide and water with release of great deal of energy in the form of ATPs.
• 2. It is the predominant respiratory pathway in most of the organisms.
• 3. Aerobic respiration is completed in four phases:
• - Glycolysis
• - Oxidation of pyruvates
• - Krebs cycle
• - Respiratory electron transport chain
• 4. Glycolysis:
• - Glycolysis is the process of breakdown of glucose or similar hexose sugar into two molecules of pyruvates through a series of enzymatic reactions releasing some energy (as ATP) and reduced coenzymes (as NADH).
• - It occurs in the cytoplasm.
• - It is completed in two phases i.e., preparatory phase and oxidative phase.
• - Preparatory phase is an investment phase in which two ATPs are consumed.
• - Its end products are two molecules of G3P.
• - Oxidative phase is pay off phase in which not only ATPs are produced through substrate level phosphorylation but it also produces NADH which upon further oxidation in respiratory electron transport chain yields more ATPs.
• - The whole glycolysis pathway takes place in the following sub steps:
• 1. Phosphorylation
• 2. Isomerization
• 3. Phosphorylation
• 4. Splitting
• 5. Isomerization
• 6. Dehydrogenation and Phosphorylation
• 7. Formation of ATP
• 8. Isomerization
• 9. Dehydration
• 10. Formation of ATP
• 5. Oxidation of Pyruvate to Acetyl-CoA:
• - Pyruvates are produced in cytosol.
• - Because pyruvate is a charged molecule, it must enter the mitochondrion via active transport with the help of the transport protein pyruvate translocase.
• - On entering the mitochondria, pyruvates do not directly participate in Krebs cycle but they undergo an intermediate phase, called oxidation of pyruvate or link reaction.
• - The oxidation of pyruvate takes place in three steps:
• 1. Decarboxylation
• 2. Oxidation/dehydrogenation
• 3. Addition of coenzyme A
• 6. Krebs Cycle:
• - This cycle was discovered by British scientist Sir Hans Krebs, therefore, called Krebs cycle.
• - It is also called Citric acid cycle or Tri carboxylic acid (TCA) cycle because the first product is citric acid.
• - Steps:
• 1. Synthesis
• 2. Dehydration
• 3. Hydration
• 4. Oxidative decarboxylation
• 5. Oxidative decarboxylation and addition of CoA
• 6. Synthesis of substrate level ATP
• 7. Dehydrogenation/oxidation
• 8. Hydration
• 9. Dehydrogenation/oxidation
• 7. Electron Transport Chain (ETC):
• - 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:
• - NADH-Q reductase or NADH-dehydrogenase complex (I)
• - FADH-dehydrogenase complex (II)
• - Coenzyme Q or Ubiquinone (mobile carrier)
• - Cytochrome reductase complex (III)
• - Cytochrome-c (mobile carrier)
• - Cytochrome oxidase complex (IV)
• 8. 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.
• - 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.
• 9. Substrate Level Phosphorylation:
• - The prime objective of cellular respiration is to generate ATPs.
• - There are two ways to do this during aerobic respiration: chemiosmosis and substrate level phosphorylation.
• - When phosphate is enzymatically transferred from an organic substrates molecule it is called substrate level phosphorylation.
• - It occurs at three occasions during aerobic respiration:
• - In glycolysis (steps 7 and 10)
• - In Krebs cycle (step 6)
• - There are four ATPs produced by this mechanism during glycolysis but two of them are supposed to be consumed in preparatory phase so net product by substrate level phosphorylation is 2 ATP.

Remember

• - Aerobic respiration = requires oxygen; 36–38 ATP
• - Four phases: Glycolysis, oxidation of pyruvate, Krebs cycle, ETC
• - Glycolysis = cytoplasm; 2 ATP, 2 NADH, 2 pyruvate
• - Oxidation of pyruvate = mitochondrial matrix; 2 acetyl-CoA, 2 CO₂, 2 NADH
• - Krebs cycle = mitochondrial matrix; 4 CO₂, 6 NADH, 2 FADH₂, 2 ATP
• - ETC = inner mitochondrial membrane; 32–34 ATP, H₂O
• - **Final products** = CO₂ + H₂O
• - ATP yield: 1 NADH = 3 ATP; 1 FADH₂ = 2 ATP
• - Total ATP: 36–38

Common Mistakes

• 1. Thinking glycolysis occurs in mitochondria – Glycolysis occurs in the cytoplasm.
• 2. Thinking Krebs cycle occurs in the cytoplasm – Krebs cycle occurs in the mitochondrial matrix.
• 3. Thinking ETC occurs in the matrix – ETC occurs in the inner mitochondrial membrane.
• 4. Confusing the ATP yield – 1 NADH = 3 ATP; 1 FADH₂ = 2 ATP.
• 5. Thinking oxygen is used in Krebs cycle – Oxygen is used in the ETC.
• 6. Thinking CO₂ is produced in the ETC – CO₂ is produced in the oxidation of pyruvate and Krebs cycle.
• 7. Confusing substrate-level phosphorylation and oxidative phosphorylation – Substrate-level = direct transfer of phosphate; Oxidative = via ETC.
• 8. Thinking ATP synthase is in the matrix – ATP synthase is in the inner mitochondrial membrane.
• 9. Forgetting the role of NADH and FADH₂ – They carry electrons to the ETC.
• 10. Thinking the Krebs cycle produces most of the ATP – The ETC produces most of the ATP.
• 11. Confusing the number of ATP produced – 36–38 ATP per glucose.
• 12. Thinking pyruvate enters mitochondria passively – Pyruvate enters via active transport.

Quick Revision

• Aerobic respiration is a catabolic process which involves the complete oxidative breakdown of organic food (especially glucose) into carbon dioxide and water with release of great deal of energy in the form of ATPs.
• It is the predominant respiratory pathway in most of the organisms.
• Aerobic respiration is completed in four phases:
• Glycolysis:
• Glycolysis is the process of breakdown of glucose or similar hexose sugar into two molecules of pyruvates through a series of enzymatic reactions releasing some energy (as ATP) and reduced coenzymes (as NADH).
• It occurs in the cytoplasm.
• It is completed in two phases i.e., preparatory phase and oxidative phase.
• Preparatory phase is an investment phase in which two ATPs are consumed.
• Its end products are two molecules of G3P.
• Oxidative phase is pay off phase in which not only ATPs are produced through substrate level phosphorylation but it also produces NADH which upon further oxidation in respiratory electron transport chain yields more ATPs.
• The whole glycolysis pathway takes place in the following sub steps:
• Oxidation of Pyruvate to Acetyl-CoA:
• Pyruvates are produced in cytosol.
• Because pyruvate is a charged molecule, it must enter the mitochondrion via active transport with the help of the transport protein pyruvate translocase.
• On entering the mitochondria, pyruvates do not directly participate in Krebs cycle but they undergo an intermediate phase, called oxidation of pyruvate or link reaction.
• The oxidation of pyruvate takes place in three steps:
• Krebs Cycle:
• This cycle was discovered by British scientist Sir Hans Krebs, therefore, called Krebs cycle.
• It is also called Citric acid cycle or Tri carboxylic acid (TCA) cycle because the first product is citric acid.
• Steps:
• Electron Transport Chain (ETC):
• 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:
• NADH-Q reductase or NADH-dehydrogenase complex (I)
• FADH-dehydrogenase complex (II)
• Coenzyme Q or Ubiquinone (mobile carrier)
• Cytochrome reductase complex (III)
• Cytochrome-c (mobile carrier)
• Cytochrome oxidase complex (IV)
• 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.
• 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.
• Substrate Level Phosphorylation:
• The prime objective of cellular respiration is to generate ATPs.
• There are two ways to do this during aerobic respiration: chemiosmosis and substrate level phosphorylation.
• When phosphate is enzymatically transferred from an organic substrates molecule it is called substrate level phosphorylation.
• It occurs at three occasions during aerobic respiration:
• In glycolysis (steps 7 and 10)
• In Krebs cycle (step 6)
• There are four ATPs produced by this mechanism during glycolysis but two of them are supposed to be consumed in preparatory phase so net product by substrate level phosphorylation is 2 ATP.

60-Second Revision

• Aerobic respiration = requires oxygen; 36–38 ATP
• Four phases: Glycolysis, oxidation of pyruvate, Krebs cycle, ETC
• Glycolysis = cytoplasm; 2 ATP, 2 NADH, 2 pyruvate
• Oxidation of pyruvate = mitochondrial matrix; 2 acetyl-CoA, 2 CO₂, 2 NADH
• Krebs cycle = mitochondrial matrix; 4 CO₂, 6 NADH, 2 FADH₂, 2 ATP
• ETC = inner mitochondrial membrane; 32–34 ATP, H₂O
• **Final products** = CO₂ + H₂O
• ATP yield: 1 NADH = 3 ATP; 1 FADH₂ = 2 ATP
• Total ATP: 36–38
• Warning: Glycolysis occurs in the cytoplasm, not mitochondria. Krebs cycle occurs in the mitochondrial matrix. ETC occurs in the inner mitochondrial membrane. Oxygen is used in the ETC, not the Krebs cycle. CO₂ is produced in the oxidation of pyruvate and Krebs cycle. Substrate-level phosphorylation is different from oxidative phosphorylation. ATP synthase is in the inner mitochondrial membrane. The ETC produces most of the ATP.