Notes on the Krebs Cycle Lecture

Overview

The Krebs cycle, also known as the citric acid cycle or Hans Krebs cycle, is a fundamental metabolic pathway discovered by Hans Adolphe Krebs in 1937, for which he received the Nobel Prize in 1953. This cycle plays a pivotal role in cellular respiration and connects the metabolism of carbohydrates, fats, and proteins. Here, organic molecules are oxidized, producing energy stored in the form of ATP (Adenosine Triphosphate).

Key Points

Definition and Significance

• Also known: Citric Acid Cycle or Hans Krebs Cycle.
• Discovered by: Hans Adolphe Krebs, 1937.
• Nobel Prize: Physiology and Medicine, 1953.
• Central Role: Connects carbohydrate, fat, and protein metabolism.
• Main Function: Releases stored energy from fats, carbohydrates, proteins through oxidation.
• Produces: ATP, NADH, FADH2 - useful for energy transfer and various cellular processes.

Biochemical Basics

• The Krebs cycle occurs in the mitochondrial matrix in eukaryotic cells and in the cytosol of prokaryotic cells.
• It begins with products generated from carbohydrates, fats, and proteins in prior metabolic pathways (e.g., glycolysis converting glucose to pyruvate).
• The cycle relies on oxidation reactions where molecules lose electrons and are broken down, releasing energy and reducing agents (NADH, FADH2).

Steps in the Krebs Cycle

1. Combination of Acetyl-CoA and Oxaloacetate:
   • Forms Citrate (6-carbon compound) catalyzed by Citrate Synthase.
2. Conversion of Citrate to Isocitrate through Isomerization:
   • Catalyzed by Aconitase.
3. Oxidative Decarboxylation of Isocitrate to Alpha-Ketoglutarate:
   • Catalyzed by Isocitrate Dehydrogenase, produces CO2 and NADH.
4. Second Oxidative Decarboxylation to Succinyl-CoA:
   • Alpha-Ketoglutarate to Succinyl-CoA (Catalyzed by Alpha-Ketoglutarate Dehydrogenase), producing NADH and CO2.
5. Conversion of Succinyl-CoA to Succinate:
   • Produces GTP and Coenzyme A, catalyzed by Succinyl-CoA Synthetase.
6. Oxidation of Succinate to Fumarate:
   • Produces FADH2, catalyzed by Succinate Dehydrogenase.
7. Hydration of Fumarate to Malate:
   • Catalyzed by Fumarase.
8. Oxidation of Malate to Oxaloacetate:
   • Produces NADH, catalyzed by Malate Dehydrogenase.

Production of Energy

• Per cycle: Produces 3 NADH, 1 FADH2, 1 GTP (converted to ATP).
• The NADH and FADH2 produced in the cycle enter the electron transport chain producing approximately:
  • 2.5 ATPs per NADH
  • 1.5 ATPs per FADH2.
• Net yield from 1 Acetyl-CoA through Krebs Cycle is approx. 10 ATPs.

Educational Tips

• Understand the precursor pathways like glycolysis and its products (e.g., pyruvate).
• Study enzyme functions and the specific reactions they catalyze.
• Keep track of carbon atoms throughout the cycle to understand how molecules transform.

Additional Resources

• Review videos on related topics like glycolysis and electron transport chain available in the provided links within the course material.
• Join course community for further discussion and resource sharing.

Conclusion

The Krebs Cycle is a critical energy-producing pathway that interlinks various metabolic processes in the cell. Understanding its components and functions is essential for studying cellular biology and biochemistry.