Original episode & show notes | Raw transcript
When we hear the word “aerobic,” many of us picture 1980s fitness classes or heart rate zone charts on a gym wall. While these are related, the scientific definition is far more fundamental. “Aerobic” simply means “in the presence of oxygen.”
The core of aerobic metabolism is the process by which our cells use oxygen to systematically break down fuel molecules—primarily carbohydrates and fats—to generate vast amounts of energy. This energy is stored in a molecule called Adenosine Triphosphate (ATP). Think of ATP as the universal energy currency for every cell in your body.
The overall chemical equation for the aerobic breakdown of a simple sugar like glucose is:
C6H12O6 (Glucose) + 6O2 (Oxygen) → 6CO2 (Carbon Dioxide) + 6H2O (Water) + ATP (Energy)
This equation looks simple, but the arrow in the middle represents a series of incredibly complex and elegant biochemical pathways. Our goal is to unpack that arrow.
Before the main aerobic engine can start, our fuel sources must be converted into a common, manageable format. Both fats and carbohydrates are processed into a two-carbon molecule called Acetyl-Coenzyme A (Acetyl-CoA).
Carbohydrates: Glucose (a six-carbon molecule) is first broken down in the cell’s main compartment (the cytosol) through a process called glycolysis. This yields two three-carbon molecules (pyruvate). Pyruvate is then shuttled into the mitochondria and converted into Acetyl-CoA, releasing one molecule of CO2 in the process.
Fats: Fats are transported into the mitochondria and undergo beta-oxidation, a process that systematically cleaves the long fatty acid chains into multiple two-carbon Acetyl-CoA molecules.
Along with Acetyl-CoA, these initial breakdown processes also generate crucial “electron carriers”—NADH and FADH₂. It’s helpful to think of these molecules as rechargeable batteries. They capture high-energy electrons and protons (H+) that are stripped from the fuel molecules and will carry them to the final stage of energy production.
The Acetyl-CoA molecules, regardless of their origin, now enter the Krebs Cycle, also known as the Citric Acid Cycle or the Tricarboxylic Acid Cycle (TCA). This cycle takes place in the innermost compartment of the mitochondria (the matrix).
The Krebs Cycle is a series of eight enzyme-catalyzed reactions that complete the breakdown of our fuel. It’s a true cycle because the final product, oxaloacetate, is also the first reactant, ready to combine with a new molecule of Acetyl-CoA and start the process over.
Here’s a simplified overview of what happens in one turn of the cycle:
Entry: A two-carbon Acetyl-CoA molecule combines with a four-carbon oxaloacetate molecule to form a six-carbon molecule, citrate.
Carbon Stripping: The six-carbon citrate molecule is progressively rearranged and broken down. In two key steps, a carbon atom is cleaved off and released as **Carbon Dioxide (CO₂) **. This is the CO₂ that we exhale.
Energy Capture: With each CO₂ release and in other steps, high-energy electrons are stripped from the intermediates. These are captured by the electron carriers, generating 3 molecules of NADH and 1 molecule of FADH₂ per turn.
Direct ATP Generation: In one step, enough energy is released to directly form one molecule of GTP (guanosine triphosphate), which is quickly converted to 1 ATP.
Regeneration: After losing two carbons as CO₂, the remaining four-carbon molecule is rearranged back into oxaloacetate, ready to accept the next Acetyl-CoA.
Key Takeaway from the Krebs Cycle: The primary purpose of this cycle is not to make a lot of ATP directly. Its main job is to finish oxidizing the carbons from our food into CO₂ and, most importantly, to load up the electron carriers (NADH and FADH₂) with high-energy electrons for the final, most productive stage. It’s crucial to note that oxygen is not used directly in the Krebs Cycle.
This is where the magic happens and where oxygen finally enters the picture. The Electron Transport Chain (ETC) is a series of four large protein complexes (Complex I-IV) embedded in the inner mitochondrial membrane.
Electron Drop-off: The fully-charged NADH and FADH₂ molecules from the previous stages arrive at the ETC and “drop off” their high-energy electrons. NADH interacts with Complex I, while FADH₂ (which holds slightly lower-energy electrons) interacts with Complex II.
Electron Cascade: The electrons are passed down the chain from one complex to the next, like a bucket brigade. Each transfer releases a small amount of energy.
Proton Pumping: The energy released as electrons move down the chain is used by Complexes I, III, and IV to actively pump protons (H+) from the mitochondrial matrix into the space between the inner and outer membranes (the intermembrane space).
Creating a Gradient: This pumping action creates a powerful electrochemical gradient. The intermembrane space becomes highly concentrated with protons (acidic, with a high positive charge), while the matrix has a low concentration (alkaline, with a negative charge). This gradient is a form of stored potential energy, much like water held behind a dam.
Oxygen’s Crucial Role: At the very end of the chain (Complex IV), the now low-energy electrons need a final destination. This is the critical role of oxygen. It acts as the final electron acceptor, combining with the electrons and some protons to form water (H₂O). Without oxygen to clear the electrons, the entire chain would back up and halt.
The potential energy stored in the proton gradient is now cashed in to make ATP. This is done by a fifth protein complex called ATP Synthase.
ATP Synthase acts like a microscopic, revolving turbine. The protons, driven by their powerful gradient, rush back into the matrix through a channel in the ATP synthase.
This flow of protons causes a part of the enzyme to spin at an incredible rate—up to 7,800 RPM.
The rotational energy of this “motor” is used to drive a chemical reaction: it physically forces a phosphate group onto an ADP (adenosine diphosphate) molecule, creating ATP.
This entire process—the movement of electrons down the ETC coupled with the synthesis of ATP—is called Oxidative Phosphorylation. It is responsible for generating the vast majority of the ATP in our bodies.
Let’s look at the final ATP tally from a single molecule of glucose:
Glycolysis: 2 ATP (anaerobic)
Krebs Cycle: 2 ATP (via GTP)
Oxidative Phosphorylation: ~26-28 ATP
Total: ~30-32 ATP per molecule of glucose.
Now compare this to a typical fat molecule (e.g., palmitate):
Fats are far more energy-dense than carbohydrates. However, the breakdown of carbohydrates is faster, making it the preferred fuel for higher-intensity exercise.
Connecting to FTP: The concept of Functional Threshold Power (FTP) in cycling represents the maximal rate at which this entire aerobic system can operate sustainably. At or below FTP, your mitochondria can effectively process the Acetyl-CoA and clear the byproducts, primarily by using oxygen to generate ATP. When you exceed FTP, your energy demand outpaces the aerobic system’s capacity. You rely more heavily on anaerobic glycolysis, leading to a rapid accumulation of metabolites that contribute to fatigue.
The most important takeaway from this detailed look at metabolism is to dispel a common myth:
It is incorrect to say that “burning fat is aerobic and burning carbs is anaerobic.”
The reality is that the complete breakdown of both fats and carbohydrates is fundamentally an aerobic process. Both fuels are converted to Acetyl-CoA, run through the Krebs Cycle, and generate ATP via the oxygen-dependent Electron Transport Chain.
The distinction is that carbohydrates can provide a small amount of energy anaerobically (through glycolysis alone), which is crucial for very high-intensity efforts. Fats, for all practical purposes, can only be metabolized aerobically. Therefore, at any sustainable endurance pace, you are aerobically metabolizing a mixture of both fats and carbohydrates.