Krebs Cycle: The 8 Reactions of Energy Metabolism and Their Role in the Human Body

The Krebs cycle is essential for producing energy in the form of ATP (It is the cell’s “energy currency”), converting molecules such as carbohydrates, fats and proteins into usable energy. Discovered by Hans Krebs, who won the Nobel Prize for Medicine in 1953, this cycle is a cornerstone of modern biochemistry.

In this article, we will analyze in detail:

• The eight chemical reactions of the cycle.
• The role of the cycle in energy production.
• How the Krebs cycle relates to other metabolic processes.
• Its implications in health and disease.

What is the Krebs Cycle, and why is it important?

The Krebs cycle is a set of chemical reactions that occur in the mitochondria of eukaryotic cells and the cytoplasm of prokaryotic cells. It serves to oxidize the acetyl-CoA, generating:

• ATP: Energy immediately usable by the cell.
• IT WASN’T FADH2: Reduced cofactors that power the electron transport chain to produce additional ATP molecules.

The cycle is essential not only for energy production but also for the synthesis of precursors used in processes such as gluconeogenesis (glucose formation), the synthesis of fatty acids, and the biosynthesis of amino acids.

The 8 Reactions of the Krebs Cycle

The Krebs cycle occurs through eight main stages, catalyzed by specific enzymes. Let’s see them in detail:

• • Citrate Synthase: Acetyl-CoA combines with oxaloacetate to form citrate.
  • This reaction releases coenzyme A, an essential metabolic cofactor.
  • Aconitation: Citrate is isomerized to isocitrate via an intermediate known as cis-aconitate.
  • Isocitrate Dehydrogenase: Isocitrate is oxidized and decarboxylated, producing alpha-ketoglutarate, NADH, and carbon dioxide.
  • Alpha-Ketoglutarate Dehydrogenase: Alpha-ketoglutarate loses another carboxyl group, forming succinyl-CoA, NADH and CO2.
  • Succinyl-CoA Synthetase: Breaking the thioester bond of succinyl-CoA produces a molecule of GTP (convertible to ATP).
  • Succinate Dehydrogenase: Succinate is oxidized to fumarate, generating a molecule of FADH2.
  • You will smoke: The fumarate is hydrated to malate.
  • Malate Dehydrogenase: Malate is oxidized to oxaloacetate, producing NADH.

At the end of the cycle, the oxaloacetate is regenerated and ready to start a new cycle.

Krebs Cycle Energy Balance

For each molecule of Acetyl-CoA that enters the cycle, the following are produced:

• 3 NADH (each generates approximately 2.5 ATP in the electron transport chain).
• 1 FADH2 (generates about 1.5 ATP).
• 1 GTP (equivalent to 1 ATP).
• 2 molecules of CO2 (expelled as a waste product).

In total, one molecule of glucose (which produces two molecules of acetyl-CoA) generates approximately 20 ATP through the Krebs cycle and oxidative phosphorylation.

Interactions with Other Metabolic Processes

The Krebs cycle does not work in isolation but is closely connected to other processes:

• • Glycolysis: It supplies pyruvate, which is converted to acetyl-CoA by pyruvate dehydrogenase.
  • Beta-Oxidation: Fatty acids are broken down to acetyl-CoA, which enters the cycle.
  • Electron Transport Chain: NADH and FADH2 transfer electrons, generating ATP.
  • Biosynthesis: Cycle intermediates, such as alpha-ketoglutarate and oxaloacetate, synthesize amino acids, nucleotides, and other biomolecules.

Regulation of the Krebs Cycle

The cycle speed is regulated by:

• Availability of substrates: Acetyl-CoA, NAD+, FAD.
• Energy levels: ATP inhibits key enzymes such as citrate synthase and isocitrate dehydrogenase.
• Ion Calcium: Stimulates enzymes such as alpha-ketoglutarate dehydrogenase in response to muscle contraction.

Role of the Krebs Cycle in Health and Disease

The Krebs cycle is involved in several pathological conditions:

• • Tumors: Tumor cells alter metabolism to promote proliferation, using alternative pathways to the Krebs cycle (Warburg effect).
  • Metabolic Diseases: Genetic defects in cycle enzymes (e.g. succinate dehydrogenase) can lead to severe disorders.
  • Diabetes: Insulin resistance affects energy metabolism, altering the efficiency of the cycle.

Scientific Curiosities

• Krebs cycle in prokaryotes: In bacteria, the cycle occurs in the cytoplasm, without mitochondrial compartments.
• Sports and Krebs Cycle: The cycle speeds up during intense exercise to meet the increased energy demand.
• Total Energy: One glucose molecule produces approximately 30-32 ATP thanks to glycolysis, the Krebs cycle and the electron transport chain.

Frequently Asked Questions (FAQ)

1. Why is it called the Krebs cycle? Because it is a cyclical process, the oxaloacetate used in the first reaction is regenerated at the end of the cycle.
2. What are the main products of the Krebs cycle? ATP, NADH, FADH2, e CO2.
3. Why does the Krebs cycle occur in the mitochondria? Mitochondria provide the ideal environment with specific enzymes and proximity to the electron transport chain.
4. How is the Krebs cycle regulated? Through the availability of substrates and the inhibition of enzymes by ATP and NADH.

Conclusion

The Krebs cycle is one of the most important biochemical processes, essential for energy production and cellular metabolism. Understanding this cycle is not only fundamental for those who study biology and medicine, but also for those who want to understand how our body generates energy to carry out all its vital functions.