Overview

Cellular respiration is the process of using oxygen in the mitochondria to chemically break down organic molecules such as glucose. This releases the energy stored in the bonds of glucose.

In this process, molecules of water and carbon dioxide are released as waste products. This series of reactions produces 36 molecules of ATP!

You can draw an analogy between the process of cellular respiration in your cells and a car. The mitochondria represent the engines of our cells where sugar is burned for fuel and the exhaust is CO₂ and H₂O. Note that if a car could burn fuel perfectly, the only exhaust should theoretically be CO₂ and H₂O as well.

However, it is important to note that mitochondria aren’t burning glucose like gasoline in a car. This would cause cells to overheat and die. Cells release the energy in glucose in a controlled, stepwise manner so that energy can be captured in a safe, effective way – by storing it in molecules of ATP.

There are three stages to Cellular Respiration. Each occurs in a specific location within the cell:

Stage	Where It Occurs
Glycolysis	Cytoplasm
Krebs Cycle (Citric Acid Cycle)	Mitochondria (matrix)
Electron Transport Chain (ETC)	Mitochondria (inner membrane, or cristae)

Examine the diagram below that shows these three stages. Notice that ATP is generated in each stage.

Aerobic Cellular Respiration

Aerobic cellular respiration occurs when the two pyruvic acid molecules from glycolysis are modified and diffuse into the mitochondria where the next two processes occur. Aerobic implies that the process requires oxygen. If there is no oxygen present after glycolysis, a process called fermentation may occur. We will discuss this in the next lesson.

Take a close look at the diagram below. Identify the areas where each step of aerobic cellular respiration occurs:

Stage 1: Glycolysis

Cellular respiration begins with glycolysis. The word “glycolysis” means to “split sugar.” In glycolysis, one molecule of glucose (6-carbon sugar) is broken in half by enzymes in the cytoplasm, producing 2 molecules of 3-carbon pyruvic acid (or, pyruvate). Splitting a molecule in half sounds simple, but glycolysis actually involves a series of steps that are controlled by specific enzymes.

Two molecules of ATP are spent to begin glycolysis, and 4 ATP are collected as energy is released from glucose. Therefore, glycolysis only gives us a net of 2 ATP. Some high energy electrons are released from glucose during this stage, making 2 NADH. Recall from the last lesson that NADH is a high energy electron carrier. We will use these electrons later (Stage 3: Electron Transport Chain) to generate even more ATP.

The diagram below illustrates the complex series of steps that are completed during glycolysis. You are not expected to know the details of each step, but you should understand what molecules go into and out of the overall process.

Let’s do a tally of cell respiration thus far. Be sure to update your Cell Respiration Notes Guide:

Stage	Where It Occurs	What Goes In	What Comes Out
Glycolysis	Cytoplasm	Glucose	2 ATP 2 NADH 2 Pyruvate Molecules

It should be noted that to move NADH from the cytoplasm into the mitochondrion for the next two stages, it costs the cell 2 ATP.  

Stage 2: The Krebs Cycle

In the presence of oxygen, the 2 molecules of pyruvic acid move from the cytoplasm into the matrix of the mitochondrion.

The Krebs cycle is a series of reactions that cycles twice, one for each molecule of pyruvate. One of the first few chemicals produced in the cycle is citric acid, which explains why the Krebs Cycle is also called the citric acid cycle.

The Krebs Cycle completely dismantles the remaining 2 pyruvates and transfers energy from them into ATP energy, energy carrier molecules, and CO₂ (the carbon and oxygen atoms originally in glucose).

The Krebs Cycle produces:

1. 2 ATP molecules
2. 8 NADH
3. 2 FADH₂
4. 6 CO₂

from each glucose molecule. The energy carrier molecules (NADH, FADH₂) move on to the next stage (Electron Transport Chain).

You may be wondering where the hydrogens in glucose have ended up? Since a hydrogen atom is made up of one proton and one electron, the electrons are now part of electron carriers, such as NADH. The protons remain in the cytoplasm or mitochondria.

Stop and Think: How does your body rid itself of the CO₂ waste from the Krebs Cycle?

Study the diagram of the Krebs Cycle below; each yellow dot is a carbon atom. Total up the number of products (ATP, NADH, FADH₂ and CO₂) from each pyruvate. Can you see why this cycle is also called the Citric Acid Cycle?

Time to update our tally chart on your Cell Respiration Notes Guide!

Stage	Where It Occurs	What Goes In	What Comes Out
Glycolysis	Cytoplasm	Glucose	2 ATP 2 NADH 2 Pyruvate Molecules
Krebs Cycle	Matrix of Mitochondria	Pyruvate -2 ATP spent to move NADH across mitochondrial membrane	2 ATP 8 NADH 2 FADH2 6 CO2

Stage 3: The Electron Transport Chain (ETC)

This stage will generate 34 ATP molecules and H₂O from the carrier molecules that were produced in the first two stages.

The electron transport chain is a group of proteins embedded in the inner mitochondrial membrane, or cristae.

There are two events in the electron transport chain:

Electron Donation (setting up a gradient):

1. High energy electrons from NADH and FADH₂ (from Stages 1 and 2) are transferred to the ETC proteins.
2. The electrons are passed along this chain of proteins and their energy is used to pump protons (H+) present in the matrix to the intermembrane space.
3. The electrons reaching the end of the chain are donated to O₂ and are used to create H₂O molecules. Oxygen is therefore the final electron acceptor.
4. This sets up a proton gradient where there are much more protons in the intermembrane space than in the matrix.

Stop and Think: Why do we breathe oxygen? What would happen if we could not supply our mitochondria with oxygen?

ATP Synthesis (making ATP):

1. The gradient created in the last step is a source of potential energy; to reach equilibrium across the membrane, the protons need a pathway. ATP Synthase is a channel protein also embedded in the membrane. Protons move back through the membrane, down their concentration gradient (passive transport).
2. ATP Synthase is also an enzyme (note that it ends in “ase”). It uses the flow of protons to generate molecules of ATP from ADP and free phosphates.
3. For each NADH, ATP synthase makes 3 ATP. For each FADH₂, ATP Synthase makes 2 ATP.

Take a look at the Electron Transport Chain in Action from the Virtual Cell Animation Collection. You aren’t expected to know the specific names of structures, but you should try to recognize the players in the video and the overall process:

• high energy electrons
• ATP
• NADPH
• water

Let’s make a final update to our tally chart. Record this in your Cell Respiration Notes Guide. Study the diagram below and use it to update your chart.

You might be wondering if we can use substances other than glucose (like the proteins or fats we eat) to get energy using cellular respiration. The answer is yes! Our bodies need to convert proteins or fats into chemicals that can enter one of the stages of cellular respiration.

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