Surely you have had to study in biology one of the most important metabolic stages in aerobic cellular respiration that takes place in our body: the Krebs cycle. It is also known as the citric acid cycle and is a critical metabolic stage that occurs in the mitochondrial matrix of animal cells. In this article, you will discover in detail the characteristics of the Krebs cycle, its step-by-step operation and its vital importance for cellular metabolism.
Cellular respiration
To understand the Krebs cycle, it is necessary to take into account that cellular respiration is divided into three fundamental phases:
- Glycolysis: Process in which glucose is broken down into pyruvate or pyruvic acid, which is then converted into Acetyl-CoA.
- Krebs cycle: Here, Acetyl-CoA is oxidized to CO2.
- Electron transport chain (also known as respiratory chain): It is the phase in which most of the energy is generated through the transfer of hydrogen electrons, taking advantage of the by-products of the previous stages.
What is the Krebs cycle?
The Krebs cycle is a crucial part of cellular metabolism and one of the main pathways by which energy is generated in the form of ATP. This cycle promotes the breakdown of the end products of carbohydrate, lipid and some amino acid metabolism. Through the Krebs cycle, Acetyl-CoA is oxidized, releasing CO2, H2O and ATP. This process is essential for our cells to obtain the energy needed to perform vital functions and physical activities. In addition, metabolic intermediates are also produced during the Krebs cycle as precursors in the biosynthesis of amino acids and other biomolecules.
Steps of the Krebs cycle
In the Krebs cycle, a series of chemical reactions allow the oxidation of Acetyl-CoA into CO2, generating high-energy molecules such as NADH, FADH2 and GTP (or ATP). These stages occur in the mitochondrial matrix and require oxygen.
- Oxidative decarboxylation of pyruvate: The process begins when pyruvate from glycolysis is converted to Acetyl-CoA through oxidative decarboxylation, producing NADH and releasing CO2.
- Formation of citrate: Acetyl-CoA combines with oxaloacetate to form citrate, the compound that gives this cycle its name.
- Conversion of citrate to isocitrate: Through an isomerization reaction catalyzed by the enzyme aconitase, citrate is converted to isocitrate.
- Oxidation of isocitrate: Isocitrate undergoes oxidative decarboxylation to α-ketoglutarate, releasing a CO2 molecule and producing NADH in the process.
- Formation of succinyl-CoA: α-Ketoglutarate is oxidized to succinyl-CoA. In this step, CO2 is also released and another molecule of NADH is generated.
- Conversion of succinyl-CoA to succinate: Through substrate-level phosphorylation, succinyl-CoA is converted to succinate, generating GTP or ATP, depending on the cell type.
- Oxidation of succinate to fumarate: Succinate is oxidized to fumarate by the action of succinate dehydrogenase, and FADH2 is produced.
- Hydration of fumarate to malate: Fumarate is converted to malate by fumarase-catalyzed hydration.
- Oxidation of malate to oxaloacetate: Finally, malate is oxidized back to oxaloacetate, regenerating the compound that is essential to restart the cycle. In addition, another molecule of NADH is generated.
The cycle repeats continuously as long as Acetyl-CoA is available, demonstrating its metabolic importance in the constant generation of energy.
History of the Krebs Cycle
Hans Adolf Krebs, a German biochemist, discovered the cycle in 1937, and his work was so influential that it earned him the Nobel Prize in 1953. Krebs demonstrated how different nutrients, such as carbohydrates, fats, and proteins, can be broken down in a single metabolic process to generate energy. His discovery provided a comprehensive understanding of how cells extract energy from food.
Importance of the Krebs cycle
The Krebs cycle is not only crucial for the production of ATP, but also generates materials that the body uses in the synthesis of biomolecules. Intermediates such as oxaloacetate and α-ketoglutarate are essential for the synthesis of amino acids, while citrate is used for the synthesis of fatty acids. In addition, the Krebs cycle is an efficient recycler: end products, such as oxaloacetate, are regenerated to start the cycle again. It is a self-sustaining system that maximizes cellular efficiency.
Products of the Krebs cycle
For each turn of the Krebs cycle, the following are generated:
- 3 NADH
- 1 FADH2
- 1 GTP (or ATP)
- 2 molecules of CO2
Both NADH and FADH2 are essential for the electron transport chain, where large amounts of ATP are produced by oxidative phosphorylation. Although the Krebs cycle does not technically generate ATP directly, GTP can be converted to ATP, and the carriers NADH and FADH2 play an essential role in the production of cellular energy. Each molecule of glucose that enters the cycle produces two molecules of Acetyl-CoA, which doubles the total amount of energy generated. All of this makes the Krebs cycle a central process not only for energy production, but also for other anabolic processes in the body. The Krebs cycle is the true heart of cellular metabolism, where energy from carbohydrates, lipids and proteins converges to be converted into the energy forms necessary for the functioning and maintenance of life. It is a fascinating process that, repeated millions of times in each of our cells, ensures that we can perform our daily functions with the necessary energy.