Lecture Notes: Detailed Overview of the Krebs Cycle

Summary

The Krebs Cycle, also known as the Citric Acid Cycle or TCA Cycle, is a vital metabolic pathway that integrates the metabolism of carbohydrates, fats, and proteins into energy production. Discovered by Hans Adolphe Krebs in 1937, this cycle is fundamental for cellular respiration, providing energy via ATP and transferring electrons through carriers like NADH and FADH2. It's central to both energy production and the generation of raw materials used in various metabolic pathways across the body.

Introduction

• Krebs Cycle is named after Hans Krebs, who received the Nobel Prize in Physiology and Medicine in 1953.
• Alternative name: Citric Acid Cycle, based on the central role of citric acid (citrate).
• Importance:
  • Central metabolic pathway connecting the breakdown products of carbohydrates, fats, and proteins.
  • Generates NADH and FADH2, crucial for ATP production.
  • Provides raw materials for other bodily processes like amino acid production.
  • Believed to be one of the oldest metabolic pathways, potentially originating abiogenically.

Conceptual Overview

• Central Metabolic Pathway:
  • Acts as a hub for converting end products of digestion (like glucose) into energy.
  • Initial pathways like glycolysis produce pyruvate, which feeds into the Krebs Cycle.
• Energy Production:
  • One molecule of glucose through glycolysis, Krebs Cycle, and the electron transport chain produces about 36 ATPs.
  • Energy is mainly derived from the oxidation of molecules.

Function and Process

• Location:
  • In eukaryotic cells: Occurs in the matrix of mitochondria.
  • In prokaryotic cells: Occurs in the cytosol.

Enzymatic Steps of the Krebs Cycle

1. Formation of Citrate:
   • Acetyl CoA (2 carbons) combines with oxaloacetate (4 carbons) to form citrate (6 carbons), catalyzed by citrate synthase.
2. Conversion to Isocitrate via Citrate Isomerization:
   • Catalyzed by aconitase.
3. Oxidation of Isocitrate to Alpha-ketoglutarate:
   • Catalyzed by isocitrate dehydrogenase, producing CO2 and NADH (oxidative decarboxylation).
4. Conversion of Alpha-ketoglutarate to Succinyl-CoA:
   • Another oxidative decarboxylation, catalyzed by alpha-ketoglutarate dehydrogenase, producing CO2, NADH.
5. Conversion of Succinyl-CoA to Succinate:
   • Produces GTP (or ATP), catalyzed by succinyl-CoA synthetase.
6. Oxidation of Succinate to Fumarate:
   • Produces FADH2, catalyzed by succinate dehydrogenase.
7. Conversion of Fumarate to Malate:
   • Catalyzed by fumarase.
8. Oxidation of Malate to Oxaloacetate:
   • Produces NADH, catalyzed by malate dehydrogenase.

Key Points

• Associations: Connects with glycolysis via pyruvate conversion to acetyl CoA.
• Electron Transport Chain Interaction:
  • NADH and FADH2 generated are key for the electron transport chain.
  • Close proximity in mitochondria facilitates efficient energy production.

Energy Outcomes

• Per Turn of Krebs Cycle:
  • Produces 3 NADH, 1 FADH2, and 1 GTP (or ATP), altering depending on the preceding metabolic stages.
  • For every glucose molecule, approximately 20 ATPs are produced in the Krebs Cycle alone.

Educational Recommendations

• Familiarize with precursor pathways like glycolysis and subsequent processes like the electron transport chain for comprehensive understanding.

Further Learning

• Additional videos on glycolysis, electron transport chain, and metabolic breakdown of fats are recommended to fully grasp the interconnectivity and functionality of these pathways.

Lecture aids

• Lecture handouts and additional resources are available on Patreon for those seeking deeper analysis or study aids.

By understanding the Krebs Cycle thoroughly, not only do we gain insight into cellular energy production but also appreciate its critical role in the broader metabolism.