Cracking the AP Biology Exam


Cellular Energetics


Aerobic respiration consists of four stages:

1. Glycolysis

2. Formation of acetyl CoA

3. The Krebs cycle

4. Oxidative phosphorylation

There are so many steps within each stage that some students find this topic too confusing to follow. Don’t sweat it. We’ve come up with a simple method to keep all the stages of cellular respiration in order: Just keep track of the number of carbons at each stage.


The first stage begins with glycolysis, the splitting (-lysis) of glucose (glyco-). Glucose is a six-carbon molecule that is broken into two three-carbon molecules, called pyruvic acid. This breakdown of glucose also results in the net production of two molecules of ATP:

Glucose + 2 ATP + 2NAD+ → 2 Pyruvic acid + 4 ATP + 2NADH

Although we’ve written glycolysis as if it were a single reaction, this process doesn’t occur in one step. In fact, it requires a sequence of reactions!

Fortunately, you don’t need to memorize these steps for the test. What you do need to know is that glucose doesn’t automatically generate ATP. It has to be activated. Once glucose is phosphorylated, it eventually splits into pyruvate.

If you take a good look at the reaction above, you’ll see two ATPs are needed to produce four ATPs. You’ve probably heard the expression, “You have to spend money to make money.” In biology, you have to invest ATP to make ATP: Our investment of two ATPs yielded four ATPs, for a net gain of two.

A second product in glycolysis is 2 NADH, which results from the transfer of H+ to the hydrogen carrier NAD+. NADH will be used elsewhere in respiration to make additional ATP.

There are four important tidbits to remember regarding glycolysis:

  • Occurs in the cytoplasm
  • Net of 2 ATPs produced
  • 2 pyruvic acids formed
  • 2 NADH produced

Once the cell has undergone glycolysis, it has two options: It can continue anaerobically, or it can switch to true aerobic respiration. As we’ll soon see, the cell’s decision has a lot to do with the environment in which it finds itself. If oxygen is present, many cells switch directly to aerobic respiration. If no oxygen is present, those same cells may carry out anaerobic respiration. Still others have no choice, and carry out only anaerobic respiration, with or without oxygen.

Since ETS is more likely to ask you about aerobic respiration, we’ll look closely at the remaining steps.

However, before we do so, let’s jump back to those important organelles, the mitochondria. We already know from our discussion in Chapter 3 that the mitochondria are the sites of cellular respiration. Now it’s time to see exactly where they manufacture ATP.

The double membrane of the mitochondria divides the organelle into four regions:

  • The matrix
  • The inner mitochondrial membrane
  • The intermembrane space
  • The outer membrane

Let’s have a look:

Why do you need to know about the different regions within a mitochondrion? Because we’ll soon see that several of the stages of aerobic respiration occur within these regions of the mitochondria—and ETS loves to ask about you questions about where things occur! Keep them in mind. We’ll be discussing them below.


When oxygen is present, pyruvic acid enters the mitochondrion. Each pyruvic acid (a three-carbon molecule) is converted to acetyl coenzyme A (a two-carbon molecule) and CO2 is released:

2 Pyruvic acid + 2 Coenzyme A + 2NAD+ → 2 Acetyl CoA+ 2 CO2 + 2NADH

Are you keeping track of our carbons? We’ve now gone from two three-carbon molecules to two two-carbon molecules. The extra carbons leave the cell in the form of CO2. Once again, two molecules of NADH are also produced.


The next stage is the Krebs cycle, also known as the citric acid cycle. Each of the two acetyl coenzyme A molecules will enter the Krebs cycle, one at a time, and all the carbons will ultimately be converted to CO2. This stage occurs in the matrix of the mitochondria.

Let’s track the carbons again. Each molecule of acetyl CoA produced from the second stage of aerobic respiration combines with oxaloacetate, a four-carbon molecule, to form a six-carbon molecule, citric acid or citrate:

Since the cycle begins with a four-carbon molecule, oxaloacetate, it also has to end with a four-carbon molecule to maintain the cycle. So how many carbons do we have to lose to keep the cycle going? Two carbons, both of which will be released as CO2. Now the cycle is ready for another turn with the second acetyl CoA.

With each turn of the cycle, three additional types of molecules are produced:

  • 1 ATP
  • 3 NADH
  • 1 FADH2

To figure out the total number of products per molecule of glucose, we simply double the number of products—after all, we started off the Krebs cycle with two molecules of acetyl CoA for each molecule of glucose!

Now we’re ready to tally up the number of ATP produced.

After the Krebs cycle, we’ve made only four ATP—two ATP from glycolysis and two ATP from the Krebs cycle.

Although that seems like a lot of work for only four ATP, we have also produced hydrogen carriers in the form of NADH and FADH2. These molecules will in turn produce lots of ATP.


We said earlier that ATP is the energy currency of the cell. While this is true, ATP is not the only molecule that stores energy. Sometimes energy is stored by electron carriers like NAD+ and FAD. (These electron carriers are also called hydrogen carriers because most electron carriers also carry hydrogen atoms.) Electrons are transferred from electron carriers to oxygen, resulting in ATP synthesis. This process is called oxidative phosphorylation.

Electron Transport Chain

As electrons (and the hydrogen atoms to which they belong) are removed from a molecule of glucose, they carry with them much of the energy that was originally stored in their chemical bonds. These electrons—and their accompanying energy—are then transferred to readied hydrogen carrier molecules. In the case of cellular respiration, these charged carriers are NADH and FADH2.

Let’s see how many “loaded” electron carriers we’ve produced. We now have:

  • Two NADH molecules from glycolysis
  • Two NADH from the production of acetyl CoA
  • Six NADH from the Krebs cycle
  • Two FADH2 from the Krebs cycle

That gives us 12 altogether.

Now let’s consider the fate of all the electrons removed from the breakdown of glucose. Here’s what happens. The electron carriers—NADH and FADH2—“shuttle” electrons to the electron transport chain, and the hydrogen atoms are split into hydrogen ions and electrons:

H2 → 2H+ + 2e

Then, two interesting things occur. First, the high-energy electrons from NADH and FADH2 are passed down the electron transport chain, which is a series of protein carrier molecules that are embedded in the cristae, the membrane along the inner membrane of a mitochondrion. Some of the carrier molecules in the electron transport chain are iron-containing carriers called cytochromes. Take a look at the entire chain below.

Each carrier molecule hands down the electrons to the next molecule in the chain. The electrons travel down the electron transport chain until they reach the final electron acceptor, oxygen. Oxygen combines with these electrons (and some hydrogens) to form water. This explains the “aerobic” in aerobic respiration. If oxygen weren’t available to accept the electrons, they wouldn’t move down the chain at all, thereby shutting down the whole process of ATP production.