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6.2 Aerobic Respiration

Stage I: Glycolysis

The word glycolysis literally means “glucose splitting,” which is exactly what happens in this stage. Enzymes split a molecule of glucose into two molecules of pyruvate (also known as pyruvic acid). Glycolysis is a complex reaction involving ten steps, each require a different enzyme.  We will not review all of the details but will summarize the key steps involved.

To start glycolysis, energy is needed to split the glucose molecule into two 3-carbon molecules. The energy  is provided by two molecules of ATP; this is called the energy investment phase. As glycolysis proceeds, energy is released and used to make four molecules of ATP; this is the energy harvesting phase. As a result, there is a net gain of two ATP molecules. During this stage, high-energy electrons are also transferred to molecules of NAD+ to produce two molecules of NADH, another energy-carrying molecule. Similar to NADPH in photosynthesis, NADH is an electron shuttle. NAD+ gains electrons (reduction) and becomes NADH, which carries the electrons to stage III of cellular respiration to make more ATP. At the end of glycolysis, there are two 3-carbon pyruvate molecules which go on to stage II of cellular respiration.

Reactants and Products of Glycolysis

Glycolysis converts glucose into two molecules of pyruvate. This releases energy, which is transferred to ATP.  Click on the hotspots to learn more.

Image Description

Glycolysis:

  • Two Pyruvate: Two pyruvates move to the next stage of cellular respiration.
  • Glucose Molecule: The 6-carbon glucose molecule is split into 2 separate 3-carbon pyruvate molecules.
  • Net gain of 2 ATP: Produces 4 ATP but uses 2 ATP, resulting in a net gain of 2 ATP released into the cell for energy use.
  • 2 NADH: Produces 2 NADH that travel to the mitochondria, carrying high-energy electrons to the ETC.

 

Exercises 6.2.1

Text Description
1. What bond and molecule store and provide energy to perform work?
  1. Bonds of glucose and an ATP molecule
  2. Bonds of ATP and a glucose molecule
  3. Bonds of a catabolic molecule and an anabolic molecule
  4. Bonds of an anabolic molecule and a catabolic molecule
2. What is the energy currency that is used by cells?
  1. ADP
  2. ATP
  3. Adenosine
  4. AMP
3. What type of molecule is the glucose that enters the glycolysis pathway split into?
  1. NADH
  2. ATP
  3. Pyruvate
  4. Phosphate

4. Used during glycolysis or produced during glycolysis?

Draggable options: ADP-used, ADP-produced, ATP-harvest, ATP-investment,  Glucose, Pyruvate, NAD+, NADH

Answers:
1.  b. Bonds of ATP and a glucose molecule
2. b. ATP
3. c. Pyruvate
4. Used during glycolysis: ADP-used, ATP-investment, Glucose, NAD+
Produced during glycolysis: ADP-produced, ATP-harvest, Pyruvate, NADH

Transition Reaction

Before pyruvate can enter the next stage of cellular respiration, it needs to be modified slightly. The transition reaction is a very short reaction which converts pyruvate into a form that the citric acid cycle can process.  Each pyruvate loses a carbon in the form of a molecule of carbon dioxide, which is released as a waste product.  The remaining 2-carbon molecule is called acetic acid.  High energy electrons are removed from acetic acid and transferred to NAD+, converting it to NADH. NADH carries the high-energy electrons to the Electron Transport Chain (stage III). Coenzyme A binds with acetic acid, forming acetyl coA, which acts as a shuttle to transport acetic acid to the mitochondria for the Citric Acid Cycle (stage II).

Note that Glycolysis (stage I) produced two molecules of pyruvate.  That means that the Transition Reaction will have to occur two times, once for each pyruvate molecule.

Reactants and Products of the Transition Reaction

In the transition reaction, pyruvate is converted to a 2-carbon molecule of acetyl CoA and a molecule of carbon dioxide. This reaction occurs twice (once for each pyruvate from Glycolysis). No ATP is produced in this stage. Click on the hotspots below to learn more.

Image Description

Transition Reaction:

  • Two Carbon Dioxide: Each pyruvate is converted into acetic acid, releasing CO₂. Two carbon dioxide diffuse out of the cell.
  • Acetyl CoA: Acetic acid combines with CoA to form Acetyl CoA. Two acetyl CoA move to the next stage of cellular respiration.
  • Two NADH: Produces two NADH (1 NADH per pyruvate, two pyruvates total). Two NADH bring high-energy electrons to the ETC.

Stage II: The Citric Acid Cycle

The citric acid cycle, also known as the Krebs cycle, consists of 8 steps which are each catalyzed by a specific enzyme. We will only summarize the key steps involved.

Acetyl coA travels to the matrix of the mitochondria for the citric acid cycle. The coA drops acetic acid off in the cycle. CoA is then  reused for cellular respiration or other metabolic processes.

In the cycle, the acetic acid combines with a four-carbon molecule called OAA (oxaloacetate). This produces citric acid, which has six carbon atoms. The citric acid goes through a series of reactions that release energy. Each of the carbons from acetic acid are stripped off OAA and released as carbon dioxide. The resulting energy is captured in molecules of NADH, ATP, and FADH2, another energy-carrying coenzyme. The final step of the Citric Acid Cycle regenerates OAA, the molecule that began the cycle. This molecule is needed for the next turn through the cycle.

Two turns of the cycle are needed because glycolysis produces two pyruvic acid molecules when it splits glucose.

Reactants and Products of the Citric Acid Cycle

In the Citric Acid Cycle, acetyl CoA is converted to two molecules of carbon dioxide. This stage occurs twice (once for each acetyl coA produced in the Transition Reaction).

Image Description

Citric Acid Cycle:

  • 4 Carbon Dioxide: Each Acetyl CoA enters the cycle, releasing 2 CO₂. Four carbon dioxide diffuse out of the cell.
  • Two ATP: Two ATP ( 1 ATP per pyruvate, two pyruvates total) are released into the cell for energy use.
  • Oxaloacetate: Acetyl CoA drops the acetic acid off onto oxaloacetate. These 2 carbons get released as 2 CO₂ and oxaloacetate remains in the cycle to be reused. This repeats for the 2nd acetyl coA, producing a total of 4 CO₂).
  • 6 NADH and 2 FADH₂: Produces 6 NADH, 2 FADH₂ (3 NADH and 1 FADH₂ per pyruvate, two pyruvates total), that bring high-energy electrons to the ETC.

 

Exercises 6.2.2

Text Description

Used or produced during the Citric Acid Cycle?

Draggable items: ADP, ATP, FAD, FADH2, NAD+, NADH, Pyruvate, Carbon Dioxide

Correct Answers:

Used during the Citric Acid Cycle: ADP, NAD+, Pyruvate, FAD

Produced during the Citric Acid Cycle: ATP, NADH, Carbon Dioxide, FADH2

Results of Glycolysis, Transition Reaction and Citric Acid Cycle

After glycolysis, the transition reaction, and the citric acid cycle, the glucose molecule has been broken down completely. All six of its carbon atoms have combined with oxygen to form carbon dioxide. The energy from its chemical bonds has been harvested but there have only been 4 ATP produced (2 from glycolysis, 2 from citric acid cycle).

The rest of the energy is currently stored in the electron carriers:

  • 10 NADH (2 from glycolysis, 2 from transition reaction, and 6 from citric acid cycle)
  • 2 FADH2 (from citric acid cycle)

This energy will be transferred to the third and final stage of cellular respiration: the Electron Transport Chain (ETC).  The ETC will use the energy from the high energy electrons to create significantly more ATP.

Stage III: Electron Transport Chain

The Electron Transport Chain (ETC) is the final stage of cellular respiration. In this stage, energy being transported by NADH and FADH2 is transferred to ATP. Oxygen acts as the final electron acceptor. It pulls the electrons out of the electron transport chain, then combines with the hydrogens released from all the NADH and FADH2, and forms water molecules. The image below summarizes the ETC. Click on the hotspots below to learn more.

Reactants and Products of the Electron Transport Chain

Image Description

Electron Transport Chain (ETC):

  • NADH and FADH₂: NADH and FADH₂ from previous stages drop high-energy electrons off at ETC, becoming NAD+ and FAD for reuse.
  • ATP:  Each NADH yields 3 ATP (10 x 3 = 30 ATP), each FADH₂ yields 2 ATP (2 x 2 = 4 ATP), total of 34 ATP produced through redox reactions
  • H₂O: O₂ serves as the final electron acceptor in the ETC, facilitating ATP production and generating water as a waste product.

Making ATP

During the ETC, high-energy electrons are released from NADH and FADH2, and they move along electron transport chains on the inner membrane of the mitochondrion. An electron transport chain is a series of molecules that transfer electrons from molecule to molecule by chemical reactions. Some of the energy from the electrons is used to pump hydrogen ions (H+) against their concentration gradient, from the matrix into the intermembrane space. Similar to what we saw in photosynthesis, this buildup of H+ has potential energy.  This gradient, known as an electrochemical gradient, drives the synthesis of ATP.

This gradient causes the ions to flow back across the membrane into the matrix, where their concentration is lower. ATP synthase acts as a channel protein, helping the hydrogen ions cross the membrane. It also acts as an enzyme, forming ATP from ADP and inorganic phosphate in a process called oxidative phosphorylation. After passing through the electron transport chain, the “spent” electrons combine with oxygen and hydrogen ions to form water.

Electron Transport Chain
Figure 6.2.1 Electron transport chains on the inner membrane of the mitochondrion carry out the last stage of cellular respiration. Image by OpenStax, CC BY 3.0
Figure 6.2.1 Description

A detailed diagram of the electron transport chain (ETC) in cellular respiration, showing the movement of electrons and protons across the inner mitochondrial membrane.

Key components in the diagram:

  • Electron transport chain (ETC) complexes (red structures): Embedded in the inner mitochondrial membrane, facilitating the transfer of electrons and pumping hydrogen ions (H⁺) into the intermembrane space.
  • ATP synthase (blue structure): A protein complex that uses the proton gradient to convert ADP and inorganic phosphate (PO₄³⁻) into ATP.
  • NADH and FADH2: High-energy electron carriers donating electrons to the ETC.
  • Flow of electrons (e⁻): Represented by yellow arrows, moving through the complexes and ultimately reducing oxygen (O₂) to form water (H₂O).
  • Proton gradient (H⁺ ions): Hydrogen ions are pumped into the intermembrane space, creating a gradient that drives ATP production.
  • ATP synthesis: ATP synthase allows H⁺ ions to flow back into the mitochondrial matrix, catalyzing the formation of ATP from ADP and phosphate.

The diagram visually represents oxidative phosphorylation, highlighting how the ETC powers ATP production through a series of redox reactions.

 

Exercises 6.2.3

Text description

Drag each item to its corresponding section.

  • Section 1: What is used during oxidative phosphorylation?
  • Section 2: What is produced during oxidative phosphorylation?

Draggable items: ADP, NAD+ and FAD, Oxygen gas, ATP, Water, NADH and FADH2

Answers:

  • Used during oxidative phosphorylation: ADP. Oxygen gas, NADH and FADH2
  • Produced during oxidative phosphorylation: ATP, Water, NAD+ and FAD

How Much ATP?

In theory, 38 molecules of ATP can be produced from the catabolism of just one molecule of glucose in aerobic respiration. Glycolysis produces two ATP molecules, and the citric acid cycle produces two more. Electron transport begins with several molecules of NADH and FADH2 and transfers their energy into as many as 34 more ATP molecules. In reality, the exact number of ATP molecules varies. Different species and even different tissues within one organism will produce different quantities of ATP.

Metabolism of molecules other than glucose

We have learned about the catabolism of glucose, which provides energy to living cells. But living things consume more than just glucose for food.

Basically, all molecules from food can enter the cellular respiration pathway somewhere. Some molecules enter at glycolysis, while others enter at the citric acid cycle. Carbohydrates, proteins, and lipids can all be converted into forms that eventually connect into glycolysis and the citric acid cycle pathways to be used for ATP production.

Exercises 6.2.4

Text Description

Place the molecules into the correct sequence of the breakdown of glucose during cellular respiration:  2 Acetyl CoA & 2 CO2, 4 Carbon Dioxide, Glucose, 2 Pyruvate.

Correct Sequence: 1.  Glucose, 2. 2 Pyruvate, 3. 2 Acetyl CoA + 2 CO2, 4. 4 Carbon Dioxide

 

Text Description
1. During cellular respiration, NADH and ATP are used to make glucose. (True/False)
2. ATP synthase acts as both an enzyme and a channel protein. (True/False)
3. The carbons from glucose end up in ATP molecules at the end of cellular respiration. (True/False)
4. Energy is stored within the chemical bonds within the glucose molecule. (True/False)
5. Cyanide inhibits cytochrome c oxidase, a component of the electron transport chain. If cyanide poisoning occurs, the pH of the intermembrane space becomes more basic. The electron transport chain can no longer pump hydrogen ions into the intermembrane space and ATP synthesis stops. (True/False)
6. What is the function of the electrons added to NAD+?
  1. They become part of a fermentation pathway.
  2. They go to another pathway for ATP production.
  3. They energize the entry of the acetyl group into the citric acid cycle.
  4. They are converted into NADP.
7. Drag the words into the correct boxes
We inhale oxygen when we breathe and exhale carbon dioxide. The oxygen we inhale is the _____ _____ _____ in the electron transport chain and allows _____ _____ to proceed, which is the most efficient pathway for harvesting energy in the form of _____ from food _____. The carbon dioxide we breathe out is _____ during the _____ when the bonds in carbon compounds are _____.
Possible answers:
  • formed
  • molecules
  • citric acid cycle
  • respiration
  • acceptor
  • ATP
  • aerobic
  • final
  • broken
  • electron

Answers:

  1. False
  2. True
  3. False
  4. True
  5. True
  6. b. They go to another pathway for ATP production.
  7. We inhale oxygen when we breathe and exhale carbon dioxide. The oxygen we inhale is the final electron acceptor in the electron transport chain and allows aerobic respiration to proceed, which is the most efficient pathway for harvesting energy in the form of ATP from food molecules. The carbon dioxide we breathe out is formed during the citric acid cycle when the bonds in carbon compounds are broken.

“4.10 Cellular Respiration” from Human Biology by Christine Miller is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, except where otherwise noted.

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Biology Essentials 1 Copyright © 2025 by Kari Moreland is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, except where otherwise noted.

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