Aerobic Cellular Respiration: How Your Body Makes Energy

‘The mitochondria is the powerhouse of the cell’. This eternal statement has and will continue to haunt countless generations of students. 

But beyond the internet meme, how does mitochondrion (yes that is the singular form of mitochondria) provide energy? The answer is through cellular respiration. From elephants to fungi, every single living thing on Earth goes through cellular respiration.

There are two kinds of cellular respiration. Aerobic (with oxygen) and anaerobic (without oxygen). This article will discuss aerobic respiration specifically in eukaryotic cells (containing a nucleus and membrane-bound organelles). 

Keep in mind a fair amount of biochemistry here was simplified and overlooked for the sake of being able to understand without needing a 4-year biology university degree and uses some technical language that may be new to you. So buckle up, put on your thinking cap, and get ready to learn!

An Overview of Aerobic Cellular Respiration and Adenosine Triphosphate

The whole purpose of cellular respiration is to turn glucose from your food into energy for your body. Aerobic cellular respiration is one of the reasons why we need oxygen to survive. Without oxygen, our bodies can’t produce enough energy to sustain ourselves. 

The chemical formula is as follows: 

Glucose + oxygen → carbon dioxide + water + energy (in the form of 36-38 ATP molecules)

Figure 1: the overall equation for aerobic cellular respiration. Sourced from Edrolo Biology Textbook Unit 3&4.

The energy produced is in the form of a molecule called Adenosine triphosphate (ATP). Water and carbon dioxide are produced as a byproduct of the reaction, with carbon dioxide being removed via diffusion into the bloodstream and exhaled from your body.

But how does ATP become energy for our body? If a cell requires energy, the ATP will sever the bond between the second and third phosphate to become adenosine diphosphate (ADP) in a process known as hydrolysis. Think of ATP as little chargeable batteries that need to be activated, while ADP are used-up batteries that no longer have power. The final step of cellular respiration is what ‘charges the battery’ and converts ADP to ATP, forming a cycle.

Fig 2: a labeled diagram of the adenosine triphosphate (ATP) and diphosphate cycle (ADP).

But hang on, isn’t there a flaw here? You've likely learned from chemistry class that breaking chemical bonds requires energy while forming chemical bonds releases energy. Shouldn’t breaking the bond between the second and third phosphate release energy? 

Well, the answer is both no and yes.

While it's true that breaking bonds require energy, water reacts with the ADP molecule and the single phosphate to form new, stronger, and stabler bonds which release a greater amount of energy than what it took to break the initial bond, resulting in a net increase in energy.

Now that we know what ATP is, it’s time to dive into the process of how it’s made. There are 3 main stages (plus a transition stage) to aerobic cellular respiration:

1. Glycolysis

   1.  Pyruvate Oxidation

2. Citric Acid cycle 

3. Electron Transport Chain and Chemiosmosis

A minuscule amount of ATP is created throughout each step, but the focus will be on the final stage, where the majority of ATP is produced.

1. Glycolysis

The first step is glycolysis, where glucose is converted into pyruvate. While your body stores glucose as fuel for energy, using glucose itself for cellular respiration would be inefficient and may be dangerous for your cells. 

Glycolysis occurs in the cytoplasm and requires a small amount of ATP to jumpstart the process. A single glucose molecule is broken apart by enzymes and is turned into 2 smaller pyruvate molecules. This process also generates 2 NADH (nicotinamide adenine dinucleotide) molecules and a net worth of 2 ATP molecules (after counting the initial ATP cost). 

NADH is a crucial coenzyme that can transfer electrons across molecules and will play a major role down the line. 

Fig. 3: ‘Glycolysis breaks the 6-carbon molecule glucose into two 3-carbon pyruvate molecules, releasing some of the chemical energy which had been stored in glucose’ (Soult, 2019).

The exact process of how glucose is broken down is complicated and it isn’t necessary to understand the basics of cellular respiration. But if you are interested in learning about it, click here for an article from Khan Academy! 

i.  Pyruvate Oxidation

The pyruvate oxidation is a transitional step after pyruvate is moved from the cytoplasm to inside the mitochondrial matrix (the space inside the inner membrane) through a process called active transport and 2 pyruvate molecules are oxidized and converted to 2 Acetyl CoA (coenzyme A).

Fig. 4: Oxidation of Pyruvate to Acetyl CoA (OpenStax College, 2016).

To understand what happens, we need to know the molecular composition of these molecules. Pyruvate is decarboxylated, meaning that a carbon atom double-bonded to an oxygen atom (also known as a carboxyl group) is removed from the molecule, and exhaled from the body in the form of carbon dioxide.

Then, for each pyruvate molecule, a NAD+ molecule bonds with a hydrogen ion, gains two electrons, and is reduced to NADH. 

• ‘Reduction’ is the gain of electrons, gain of oxygen, gain of hydrogen, or loss of oxygen. Conversely, ‘oxidation’ is the counterpart to reduction, referring to the loss of electrons, loss of oxygen, loss of hydrogen, or gain of oxygen.

• Most hydrogen atoms do not contain neutrons. Thus, a hydrogen ion [H+] is simply just a proton.

2. Citric Acid Cycle  

The citric acid cycle, also known as the Krebs cycle for the person who discovered it, is a series of enzymatic reactions where glucose is fully oxidized. The result is that a single glucose molecule (or 2 acetyl CoA) forms 2 ATP, 6 NADH, and 2 FADH2 (Flavin adenine dinucleotide) inside the mitochondrial matrix.

• FADH2 is a coenzyme similar to NADH that also ‘assists in transferring electrons’.

Acetyl CoA loses CoA and combines with oxaloacetate (a 4-carbon enzyme) to form citrate (a 6-carbon molecule). Citrate then slowly loses carbons through oxidation, which forms carbon dioxide and is exhaled.  NAD+ and FAD+ molecules use the electrons and hydrogen ions made available from this oxidation to form NADH and FADH2. 

This process is a closed loop, with the final molecule, oxaloacetate, being used to form the first molecule, citrate. The process of forming citrate also creates a byproduct of citric acid, giving the ‘citric acid cycle’ its name.

Fig. 5: a simplified diagram showing the steps involved a single citric acid cycle, featuring GTP.

3. Oxidative phosphorylation: Electron Transport Chain and Chemiosmosis

Up until now, your body has focused on producing FADH2 and NADH rather than ATP. This is because these two coenzymes play key roles in producing ATP through the electron transport chain.

The electron transport chain is a series of progressively lower-energy protein complexes that NADH and FADH2 donate high-energy electrons to. Electrons want to be as stable as possible and release excess energy as they transition to a lower state of energy. Your cells use this released energy to forcefully pump protons (using specific protein complexes) across the mitochondria’s inner membrane (from the mitochondrial matrix to intermembrane space (IMS), see Fig. 7). This creates an imbalance of protons, known as the proton gradient. There’s a high concentration of protons in the IMS, and they want to move back into a lower concentration (mitochondrial matrix). A common analogy is to imagine water (high concentrations of protons in the IMS) inside a dam (inner membrane) that is held back from flowing down the river (into the matrix).

Fig. 6: (left picture) a simplified diagram of oxidative phosphorylation.  Electron transport chain (red). Chemiomosis (blue).

Fig. 7: (right picture) a cut diagram of the components of the mitochondria.

Chemiosmosis

However, the proton complexes are a one-way trip and the only way back into the matrix is through an enzyme called ATP synthase. The flow of protons in the gradient rotates the ATP synthase enzyme, powering it to convert ADP to ATP by bonding a third phosphate.

Finally, to prevent clogging the system, oxygen is used as a terminal electron acceptor. It is the last molecule to receive an electron in oxidative phosphorylation and is combined with hydrogen ions to produce water [H2O], releasing energy as it forms new bonds.

A single NADH molecule can produce around 3 ATP molecules. While the previous steps (glycolysis, pyruvate oxidation, Krebs cycle) of cellular respiration make up a sum of approximately ~4 ATP molecules, the electron transport chain and chemiosmosis alone make up a whopping 30-32 ATP molecules!

In total, a single glucose molecule can fuel the production of up to ~36-38 ATP molecules.

• The electron transport chain and chemiosis are incredibly intricate reactions. Click here if you’re interested to learn more about them!

Summary of Cellular Respiration 

In summary, the process of aerobic eukaryotic cellular respiration for a single glucose molecule: 

1. Glycolysis, where glucose is converted into the more efficient form of 2 pyruvate molecules and produces 2 ATP and 2 NADH.

2. 2 pyruvates are oxidized, forming 2 Acetyl CoA and producing 2 NADH.

3. The citric acid cycle completely oxidizes glucose and produces numerous enzymes, with 6 NADH and 2 FADH.

4. NADH and FADH2 donate excited electrons to the electron transport chain, releasing energy which is used to pump protons into the IMS to form a proton gradient. The flow of protons powers ATP synthase which converts ADP into ATP. In total, your body produces ~36-38 ATP molecules.

TLDR: the goal of cellular respiration is to make ATP by converting glucose into a workable substance, producing as much NADH and FADH2 as possible, and using the coenzymes to donate electrons to power the electron transport chain, which generates the proton gradient to drive the ATP synthase enzyme.

Comparison of photosynthesis and aerobic respiration

If the chemical equation of aerobic respiration looked familiar to you, you’ve likely seen it before, simply in reversed order. Photosynthesis and aerobic respiration have exactly the same components, simply with their reactants and products swapped.

Fig. 8: the chemical equation for photosynthesis (reading left to right) and aerobic cellular respiration (reading right to left)

Aerobic respiration is a combustion reaction, breaking down glucose to produce energy (in the form of ATP) with water and carbon dioxide as a byproduct.

On the other hand, photosynthesis is a combination reaction, combining carbon dioxide and water to form glucose, with oxygen as a byproduct (fueled by sunlight).

In photosynthesis, glucose is made to create energy, whereas in cellular respiration, glucose is destroyed to gain energy. Plants are capable of both chemical reactions, where they make glucose using photosynthesis, and then break it down to make ATP using cellular respiration.  This is because unlike humans plants are unable to digest cake, so they must make their own food instead.

Fun Facts

• Cellular respiration is a slow combustion reaction, where glucose is the fuel! 

• Glucose + oxygen - > carbon dioxide + water + energy 

• Cyanide poisoning works by blocking a step in the electron transport chain, preventing the majority of ATP from being produced.

• The exact amount of ATP produced depends on a variety of factors, including genetics, physical health, and lifestyle.

Conclusion

Cellular respiration is a complex and fascinating process that powers and produces the energy of all the living creatures on earth, from tiny ants on land to the colossal blue whales in the ocean. 

Now, not only do you know that the ‘mitochondria is the powerhouse of the cell’, but also the why and how it provides energy through cellular respiration. So pat yourself on the back for dealing with so much scientific jargon and learning the intricate system of how our cells produce adenosine triphosphate!

Bibliography

Amoeba Sisters (2021). Cellular Respiration (UPDATED). [online] www.youtube.com. Available at: https://www.youtube.com/watch?v=eJ9Zjc-jdys.

Biology LibreTexts. (2016). 2.27: Glycolysis. [online] Available at: https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Introductory_Biology_(CK-12)/02%3A_Cell_Biology/2.27%3A_Glycolysis.

Brody, T. (2020). Krebs cycle - an overview. [online] www.sciencedirect.com. Available at: https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/krebs-cycle.

Cooper, G.M. (2000). The Mechanism of Oxidative Phosphorylation. The Cell: A Molecular Approach. 2nd edition, [online] 2(2). Available at: https://www.ncbi.nlm.nih.gov/books/NBK9885/.

CrashCourse (2012). ATP & Respiration: Crash Course Biology #7. YouTube. Available at: https://www.youtube.com/watch?v=00jbG_cfGuQ [Accessed 2 Apr. 2019].

Gentry, K., Craig, A., Furness, T., Liu, H., Sparks, C., Disher, J., Koschitzke, E., Nguyen, G. and Komesaroff, R. (2022). Edrolo VCE Biology. Units 3 & 4. 2nd ed. Fitzroy, Vic.: Edrolo, pp.298–306.

Jove.com. (2025). JoVE | Peer Reviewed Scientific Video Journal - Methods and Protocols. [online] Available at: https://app.jove.com/science-education/11008/atp-yield-from-glucose-catabolism [Accessed 5 Jan. 2025].

Northern Arizona University (n.d.). ATP and ADP. [online] www2.nau.edu. Available at: https://www2.nau.edu/lrm22/lessons/atp/atp.html.

OpenStax College, Biology (2016). Oxidation of Pyruvate and the Citric Acid Cycle. [Online Image] openStax. Available at: https://openstax.org/books/biology/pages/1-introduction.

Soult, A. (2019). Diagram of glucose breaking down into pyruvate. [Online Image] LibreTexts Chemistry. Available at: https://chem.libretexts.org/Bookshelves/Introductory_Chemistry/Chemistry_for_Allied_Health_%28Soult%29/15%3A_Metabolic_Cycles/15.01%3A_Glycolysis [Accessed 25 Jan. 2025].

Study.com. (n.d.). FADH2 & NADH: Definition & Overview - Video & Lesson Transcript. [online] Available at: https://study.com/academy/lesson/fadh2-nadh-definition-lesson-quiz.html.