Aerobic respiration is a metabolic process by which organic molecules, such as glucose, are converted into energy in the form of adenosine triphosphate (ATP) in the presence of oxygen. Aerobic respiration is highly efficient and allows cells to produce a large amount of ATP compared to other metabolic processes.

The key part of aerobic respiration is that it requires oxygen to occur. It is different from anaerobic respiration, which does not require oxygen to occur and produces far less ATP.

What are the four stages of aerobic respiration?

Aerobic respiration is the primary method by which cells derive energy from glucose and is prevalent in most organisms, including humans. Aerobic respiration involves four several stages:

1. Glycolysis
2. The link reaction
3. The Krebs cycle, also known as the citric acid cycle
4. Oxidative phosphorylation.

During these stages, glucose is broken down into carbon dioxide and water, releasing energy that is captured in ATP molecules. Let's have a look at each step in particular.

Glycolysis in aerobic respiration

Glycolysis is the first step of aerobic respiration and occurs in the cytoplasm. It involves splitting a single, 6-carbon glucose molecule into two 3-carbon pyruvate molecules. During glycolysis, ATP and NADH are also produced. This first step is also shared with anaerobic respiration processes, as it does not require oxygen.

There are multiple, smaller, enzyme-controlled reactions during glycolysis, which occur in four stages:

1. Phosphorylation of glucose - Prior to being split into two 3-carbon pyruvate molecules, glucose needs to be made more reactive. This is done by adding two phosphate molecules, which is why this step is referred to as phosphorylation. We get the two phosphate molecules by splitting two ATP molecules into two ADP molecules and two inorganic phosphate molecules (Pi) (\(2ATP \rightarrow 2 ADP + 2P_i\)). This is done via hydrolysis, which means that water is used to split ATP. This then provides the energy needed to activate glucose, and lowers the activation energy for the next enzyme-controlled reaction.
2. Splitting of phosphorylated glucose - In this stage, each glucose molecule (with the two added Pi groups) is split into two. This forms two molecules of triose phosphate, a 3-carbon molecule.
3. Oxidation of triose phosphate - Once these two triose phosphate molecules are formed, hydrogen is removed from them both. These hydrogen groups are then transferred to a hydrogen-carrier molecule, NAD+. This forms reduced NAD or NADH.
4. ATP production - Both of the triose phosphate molecules, newly oxidised, are then converted into another 3-carbon molecule known as pyruvate. This process also regenerates two ATP molecules from two molecules of ADP.

Fig. 2. Steps in glycolysis. As we mentioned above, glycolysis is not a single reaction but rather takes place in several steps that always happen together. So to simplify the process of aerobic and anaerobic respiration, they are bundled together under "glycolysis".

The overall equation for glycolysis is:

\[C_6H_{12}O_6 + 2ADP + 2 P_i + 2NAD^+ \rightarrow 2C_3H_4O_3 + 2ATP + 2 NADH\]

Glucose Pyruvate

The link reaction in aerobic respiration

During the link reaction, the 3-carbon pyruvate molecules produced during glycolysis undergo a series of different reactions after being actively transported into the mitochondrial matrix. The following reactions are:

1. Oxidation - Pyruvate is oxidised into acetate. During this reaction, pyruvate loses one of its carbon dioxide molecules and two hydrogens. NAD takes up the spare hydrogens and reduced NAD is produced (NADH). The new 2-carbon molecule formed from pyruvate is called acetate.
2. Acetyl Coenzyme A production - Acetate then combines with a molecule called coenzyme A, which is sometimes shortened to CoA. 2-carbon Acetyl Coenzyme A is formed.

Overall, the equation for this is:

\[C_3H_4O_3 + NAD + CoA \rightarrow Acetyl \space CoA + NADH + CO_2\]

Pyruvate Coenzyme A

The Krebs cycle in aerobic respiration

The Krebs cycle is the most complex of the four reactions. Named after the British biochemist Hans Krebs, it features a sequence of redox reactions that occur in the mitochondrial matrix. The reactions can be summarised in three steps:

1. The 2-carbon acetyl coenzyme A, which was produced during the link reaction, combines with a 4-carbon molecule. This produces a 6-carbon molecule.
2. This 6-carbon molecule loses a carbon dioxide molecule and a hydrogen molecule through a series of different reactions. This produces a 4-carbon molecule and a single ATP molecule. This is a result of substrate-level phosphorylation.
3. This 4-carbon molecule has been regenerated and can now combine with a new 2-carbon acetyl coenzyme A, which can begin the cycle again.

\[2 Acetyl \space CoA + 6NAD^+ + 2 FAD +2ADP+ 2 P_i \rightarrow 4 CO_2 + 6 NADH + 6 H^+ + 2 FADH_2 + 2ATP\]

These reactions also result in the production of ATP, NADH, and FADH₂ as by-products.

Fig. 3. Krebs cycle diagram.

Oxidative phosphorylation in aerobic respiration

This is the final stage of aerobic respiration. The hydrogen atoms released during the Krebs cycle, along with the electrons they possess, are carried by NAD⁺ and FAD (cofactors involved in cellular respiration) into an electron transfer chain. The following stages occur:

1. After the removal of hydrogen atoms from various molecules during glycolysis and the Krebs cycle, we have a lot of reduced coenzymes such as reduced NAD and FAD.
2. These reduced coenzymes donate the electrons that these hydrogen atoms are carrying to the first molecule of the electron transfer chain.
3. These electrons move along the electron transfer chain using carrier molecules. A series of redox reactions (oxidation and reduction) occurs, and the energy that these electrons release causes the flow of H+ ions across the inner mitochondrial membrane and into the intermembrane space. This establishes an electrochemical gradient in which H+ ions are flowing from an area of higher concentration to an area of lower concentration.
4. The H+ ions build up in the intermembrane space. They then diffuse back into the mitochondrial matrix through the enzyme ATP synthase, a channel protein with a channel-like hole that protons can fit through.
5. As the electrons reach the end of the chain, they combine with these H+ ions and oxygen, forming water. Oxygen acts as the final electron acceptor, and ADP and Pi combine in a reaction catalysed by ATP synthase to form ATP.

The overall equation for aerobic respiration is the following:

\[C_6H_{12}O_6 + 6O_2\rightarrow 6H_2O + 6CO_2\]

Glucose Oxygen Water Carbon dioxide

Aerobic respiration equation

As we have seen, aerobic respiration consists of a lot of consecutive reactions, each with its own regulating factors, and particular equations. However, there's a simplified way to represent aerobic respiration. The general equation for this energy-producing reaction is:

Glucose + oxygen \(\rightarrow\) Carbon dioxide + water + energy

or

C₆H₁₂O₆ + 6O₂ + 38 ADP + 38 P_i \(\rightarrow\) 6CO₂ + 6H₂O + 38 ATP

Where does aerobic respiration take place?

In animal cells, three of the four stages of aerobic respiration take place in the mitochondria. Glycolysis occurs in the cytoplasm, which is the liquid that surrounds the cell’s organelles. The link reaction, the Krebs cycle and oxidative phosphorylation all take place within the mitochondria.

As displayed in Fig. 4 the mitochondria’s structural features help to explain its role in aerobic respiration. The mitochondria have an inner membrane and an outer membrane. This double membrane structure creates five distinct components within the mitochondria, and each of these aids aerobic respiration in some way. We will outline the main adaptations of the mitochondria below:

• The outer mitochondrial membrane allows for the establishment of the intermembrane space.
• The intermembrane space enables the mitochondria to hold protons that are pumped out of the matrix by the electron transport chain, which is a feature of oxidative phosphorylation.
• The inner mitochondrial membrane organises the electron transport chain, and contains ATP synthase which helps convert ADP to ATP.
• The cristae refer to the infoldings of the inner membrane. The cristae’s folded structure helps to expand the surface area of the inner mitochondrial membrane, which means that it can produce ATP more efficiently.
• The matrix is the site of ATP synthesis and is also the location of the Krebs cycle.

What are the differences between aerobic and anaerobic respiration?

Although aerobic respiration is more efficient than anaerobic respiration, having the option to produce energy in the absence of oxygen is still important. It allows organisms and cells to survive in suboptimal conditions, or to adapt to environments with low oxygen levels.