• Introduction
  • The basics of aerobic respiration
  • Aerobic glycolysis
  • The citric acid cycle
  • Oxidative phosphorylation
  • Fatty acid oxidation
  • Amino acid oxidation
  • Final thoughts
  • Sources
  • Aerobic respiration: producing energy (ATP) with the presence of oxygen.
  • Adenosine triphosphate: ATP is a molecule that carries energy within cells.
  • Anaerobic respiration: producing energy (ATP) without the presence of oxygen.
  • Citric acid cycle: a series of chemical reactions used by all aerobic organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats, and proteins into carbon dioxide.
  • Electron carrier: Small organic molecules that switch between oxidized and reduced forms and transport electrons during metabolic reactions
  • Glycolysis: the breakdown of glucose, which releases energy and produces two molecules of pyruvate, ATP, NADH, and water.
  • Lactate: a byproduct of anaerobic respiration. Known to cause fatigue and nausea.
  • Maximum oxygen uptake: The maximum amount of oxygen a person can use during intense exercise.
  • NAD+: An oxidized form of Nicotinamide adenine dinucleotide that accepts electrons from other reactions and becomes reduced.
  • NADH: A reduced form of Nicotinamide adenine dinucleotide that carries electrons from one reaction to another. An important cofactor in metabolism consisting of two nucleotides and their phosphate groups.
  • Pyruvate: The end product of glycolysis, and an important molecule in multiple biological pathways, such as the citric acid cycle.

Introduction

Energy metabolism refers to complex processes where nutrients are broken down to produce energy in the form of adenosine triphosphate (ATP). This can be divided into three separate systems; aerobic respiration, anaerobic respiration, and the phosphagen system.

Each of these systems has a specific function and process in producing energy. This energy is used during exercise as well as maintaining regular bodily functions, including cell regeneration, hormone activity, heartbeat, breathing, etc.

Aerobic respiration is the slowest of the energy production mechanisms. However, it is estimated that approximately 95% of ATP required during rest or light exercise is made aerobically, making it the most efficient way to produce energy. A fully oxidized glucose molecule produces a total of 30-32 molecules of ATP (compared to two molecules through anaerobic respiration). 

This post explains the basic mechanisms of aerobic respiration and what makes it so essential for athletic performance.

The basics of aerobic respiration

Aerobic respiration, also known as aerobic energy production, refers to breaking down blood glucose, stored muscle glycogen, and fatty acids into ATP with the presence of oxygen. This process also produces water and carbon dioxide as by-products. These do not hinder the muscles’ ability to contract like the lactic acid produced through anaerobic respiration.

In eukaryotes (cells with organelles) aerobic respiration takes place in the mitochondria. There, a glucose molecule is fully oxidized to produce vast amounts of ATP. However, this energy system is also slow to start and requires enough oxygen to work. The system itself can be divided into three separate processes; aerobic glycolysis, the citric acid cycle, and oxidative phosphorylation.

  • Aerobic glycolysis: in this first stage of aerobic metabolism, carbohydrates in the form of glycogen or glucose are broken down with oxygen into pyruvate. This also produces two molecules of ATP.
  • The citric acid cycle: in this second phase of aerobic respiration, pyruvate enters the mitochondria and is converted into citrate. This produces two molecules of ATP as well as hydrogen that are later used in oxidative phosphorylation.
  • Oxidative phosphorylation: in this last stage of aerobic respiration, the hydrogen ions released in the citric acid cycle enters the electron transport chain inside the mitochondria. This final stage produces 34 molecules of ATP.

While aerobic respiration is not the fastest way to produce ATP, it is the main source of energy during longer endurance activities. This is because the aerobic system utilizes a nearly endless resource of carbohydrates and fat. These carbohydrates are usually fully depleted in 90 minutes of exercise, after which fat takes its place as the main source of fuel. Although these systems are conceptually different, all of them are used simultaneously during exercise and rest. The only thing that changes is how big of a portion each has on total energy production. 

Duration

Classification

Energy Source

1-3s

Anaerobic

Stored ATP

3-10s

Anaerobic

ATP + CP

10-45s

Anaerobic

ATP + CP + Muscle Glycogen

45s-2mins

Anaerobic, Lactic

Muscle Glycogen

2-4mins

Aerobic + Anaerobic

Muscle Glycogen + Lactic Acid

>4mins

Aerobic

Muscle Glycogen + Fatty Acids

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Aerobic Energy System

With oxygenOccurs in the mitochondriaSlow energy productionVast energy storages(glucose, protein & fat)Does not produce lactic acid

Aerobic glycolysis

Glycolysis gets its name from the Greek words of glyk (sweet) and lysis (dissolution). Therefore, it is accurately named to describe the process of breaking down simple sugars (glucose, fructose, galactose) into a form of fuel that your body can use. Interestingly, the first stage of this process is anaerobic (does not require oxygen) and occurs in the cytoplasm of the cell. How the byproducts of this process are used later depends on the availability of sufficient oxygen.

Aerobic glycolysis starts by breaking down a six-carbon glucose molecule (C₆H₁₂O₆) derived from blood glucose or muscle glycogen into two three-carbon molecules of pyruvate (CH3COCOO−). This process produces two molecules of ATP, a hydrogen ion (H+), and NADH, which can further be used in oxidative phosphorylation. 

Glucose + 2 NAD+ + 2 Pi + 2 ADP

2 Pyruvate + 2 NADH + 2 H+ + 2 ATP + 2 H2O

In eukaryotic cells which contain mitochondria, pyruvate molecules are decarboxylated by pyruvate dehydrogenase complex. In simple terms, pyruvate is removed from its carboxyl group, producing carbon dioxide (CO2) as a byproduct. This process is more commonly known as link creation. 

1 Pyruvate + 1 NAD+ + CoA

1 Acetyl-CoA + NADH + CO2 + H+

More importantly, this process produces acetyl-CoA (C23H38N7O17P3S) which is an integral part of the citric acid cycle. Thus, allowing the oxidation of glucose to continue. 

The citric acid cycle

The citric acid cycle, also called the Krebs cycle, is the second stage of aerobic respiration. Unlike glycolysis, which takes place in the cytoplasm of the cell, the citric acid cycle occurs in the mitochondria. 

In aerobic conditions, the pyruvate molecules produced through glycolysis are oxidized by an enzyme called pyruvate dehydrogenase. This produces a two-carbon molecule called acetyl-CoA as well as carbon dioxide. The main function of acetyl-CoA is delivering an acetyl group into the citric acid cycle to be oxidized to produce more ATP. 

The citric acid cycle consists of eight stages of redox, dehydration, hydration, and decarboxylation reactions where Acetyl-CoA is ultimately oxidized to CO2. In the first step of the process, acetyl-CoA attaches itself to oxaloacetate (C4H4O5), which is a four-carbon molecule. This produces a six-carbon molecule called citrate (Na3C6H5O7).

Oxaloacetate + Acetyl-CoA

Citrate

These citrate molecules are oxidized after several reactions, and they release two molecules of CO2 for every acetyl group that enters the citric acid cycle. This process also reduces three molecules of NAD+ to NADH, one FAD to FADH₂, as well as produces one molecule of GTP (guanine diphosphate). Also keep in mind that a single glucose molecule produces two molecules of acetyl-CoA, meaning that the total amount of molecules produced by the citric acid cycle is doubled.

Citrate

2 CO₂ + 3 NADH + 1 FADH₂ + 1 GTP

Interestingly, the last metabolic pathway of the citric acid cycle regenerates oxaloacetate, which is also the same molecule used at the beginning of the cycle. This continuous cycle of generating ATP is the reason why the citric acid cycle is considered a closed loop.

By itself, the citric acid cycle produces a relatively insufficient amount of ATP. However, it also produces high-energy coenzymes NADH and FADH₂ which work as electron carriers that drive the electron transport chain and oxidative phosphorylation. Thus, allowing the oxidation of glucose to continue for increased ATP production. 

Oxidative phosphorylation

Oxidative phosphorylation is the final phase of aerobic respiration. Like the other phases of aerobic respiration, oxidative phosphorylation also occurs in the mitochondria. This process can be roughly divided into two stages; 

  • Oxidation of NADH and FADH₂
  • Phosphorylation of ADP to ATP

Oxidative phosphorylation begins with the byproducts of the citric acid cycle. More specifically, the two electron carriers called NADH and FADH₂. NADH especially has the potential to produce significant amounts of ATP when fully oxidized. 

However, this energy cannot be released all at once. Instead, NADH and FADH₂ are oxidized, forcing them to release their electrons and passing them to a series of four protein complexes called the electron transport chain. The released electrons then flow through the electron transport chain, causing them to gradually release energy as they move from one protein complex to another. This released energy is also used to pump hydrogen ions (H+), also known as protons, from the mitochondrial matrix through the inner mitochondrial membrane into the intermembrane space.

NADH & FADH₂

H+ + NAD+ + 2 e- &  FAD + 2 H+ + 2 e-

Released electrons to electron transport chain

As hydrogen ions are pumped out of the mitochondrial matrix, they create an outward current and develops electric potential across the mitochondrial membrane. The difference in charge on either side of the membrane is called an electrochemical gradient. Through simple diffusion, these ions will move across the membrane from a higher concentration to a lower concentration carrying electric potential. 

As the hydrogen ions flow back into the mitochondrial matrix, they create chemiosmotic potential, also known as a proton motive force. This fuels an enzyme called ATP synthase that catalyzes the formation of ATP from ADP (adenosine diphosphate) and inorganic phosphate (Pi). This entire process of delivering hydrogen ions across a semipermeable membrane is known as chemiosmosis. 

ADP + Pi + 2H+out

ATP + H2O + 2H+in

This final stage of aerobic respiration maximizes the ATP yield of a single glucose molecule and generates 30-32 molecules of ATP. 

Aerobic respiration uses blood glucose, muscle glycogen, and, fatty acids to produce energy.

Fatty acid oxidation

The body has a significant amount of energy stored in the adipose tissue as fat. When glucose levels are running low, such as during starvation or long and strenuous activity, these triglycerides can be broken down into fatty acids and glycerol. This process is called lipolysis, and it takes place in the cytoplasm.

While the released glycerol can enter the glycolysis as DHAP (C3H7O6P), fatty acids can be converted into acetyl-CoA. This process is known as beta-oxidation. Acetyl-CoA is also the same molecule used in the citric acid cycle to produce ATP. 

Triglycerides have a significantly higher energy yield (~106 ATP for one molecule of palmitate) than glucose or amino acids. This is because a single triglyceride molecule consists of three fatty acid molecules with 16-20 carbons in each one. Therefore, fatty acid oxidation offers a large portion of energy to the heart, kidneys, and skeletal muscles during physical activity or when glucose levels are low. This also prevents having to break down muscle tissue for energy during longer exercises.

Let’s look at a marathon as an example. During a 42.2km (26.2mi) race, your body’s glycogen storage (103 mol of ATP at best) is not enough to provide the 150 mol of ATP needed to cross the finish line. Therefore, it is crucial that your muscles are able to utilize other means to generate energy for the working muscles. Another thing to keep in mind is that ATP is produced much faster from limited storage than high capacity ones (CP production being 10 times faster). While fatty oxidation is slow to start, it is the biggest energy reserve in the body. 

Amino acid oxidation

Although protein is rarely used for energy production, it does occur during long periods of starvation or strenuous exercise when sufficient energy cannot be produced from carbohydrates or fat. 

Because body proteins do not contain glucose or triglycerides that can be used for fuel, these proteins must sometimes be broken down into amino acids. This process is known as proteolysis. 

Processing these amino acids creates a large number of important metabolic intermediates that can be used either directly or indirectly as by the citric acid cycle. These include pyruvate, acetyl-CoA, acetoacetyl-CoA, oxaloacetate, and α-ketoglutarate.

Fatty acids are used for energy when glucose levels are running low.

Final thoughts

Aerobic respiration is a very complex process and requires an in-depth look to fully comprehend. With this in mind, it is not surprising that the research in cellular respiration has resulted in two Nobel prizes: Peter D. Mitchell for his chemiosmotic hypothesis, explaining the process of oxidative phosphorylation, and Hans Krebs for discovering the citric acid cycle in 1953.

The good thing is, you don’t need to know every detail about energy metabolism in everyday life or when trying to improve your athletic performance. To put it in simple terms, the nutrients derived from food are broken down into a form of energy your body can use. Whether this is done aerobically or anaerobically depends on how much oxygen is available. 

You should also keep in mind that energy production mechanisms do not immediately go from one system to another. In fact, they have a significant amount of overlap. For example, during short and intense exercises, the majority of the energy is produced via the phosphagen system and the anaerobic energy system. On the other hand, the aerobic system becomes increasingly important during longer physical performances.

Did you learn anything new about aerobic respiration? Let us know in the comments.

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