Lecture Notes: The Krebs Cycle

Introduction

• The Krebs Cycle: Also known as the Citric Acid Cycle or the Tricarboxylic Acid Cycle.
• Importance: Part of cellular respiration aimed at producing ATP.
• Prerequisite: Understanding of glycolysis.

Glycolysis Recap

• Glucose (C6H12O6) is broken down into two pyruvate molecules (3 carbons each).
• Produces 2 NADH and 2 ATP.
• Pyruvate enters mitochondria to continue to the Krebs cycle.

Transformation of Pyruvate to Acetyl CoA

• Pyruvate (3C) transforms into Acetyl CoA (2C).
• Loses a carbon as CO2 and gains coenzyme A (CoA).
• Requires NAD+ converting to NADH + H+.
• Enzyme: Pyruvate Dehydrogenase.
• Involves B vitamins:
  • B1: Thiamine Pyrophosphate (TPP)
  • B5: Pantothenic Acid
  • B3: Niacin for NAD+

Steps of the Krebs Cycle

1. Formation of Citrate

   • Acetyl CoA (2C) binds with Oxaloacetate (4C) to form Citrate (6C).
   • Enzyme: Citrate Synthase.

2. Conversion to Isocitrate

   • Citrate rearranges to Isocitrate (6C) using enzyme Aconitase.

3. Formation of Alpha-Ketoglutarate

   • Isocitrate loses a carbon as CO2 to form Alpha-Ketoglutarate (5C).
   • Enzyme: Isocitrate Dehydrogenase.
   • Converts NAD+ to NADH.

4. Conversion to Succinyl CoA

   • Alpha-Ketoglutarate loses another carbon as CO2 and gains CoA.
   • Enzyme: Alpha-Ketoglutarate Dehydrogenase.
   • Converts NAD+ to NADH.

5. Formation of Succinate

   • Succinyl CoA releases CoA becoming Succinate (4C).
   • Produces ATP or GTP via substrate-level phosphorylation.
   • Enzyme: Succinyl CoA Synthetase.

6. Conversion to Fumarate

   • Succinate is converted to Fumarate (4C).
   • Converts FAD to FADH2.
   • Enzyme: Succinate Dehydrogenase.

7. Conversion to Malate

   • Fumarate becomes Malate (4C) using enzyme Fumarase.

8. Regeneration of Oxaloacetate

   • Malate converts back to Oxaloacetate (4C).
   • Converts NAD+ to NADH.
   • Enzyme: Malate Dehydrogenase.

Products of the Krebs Cycle

• For each glucose molecule (2 cycles):
  • 4 CO2
  • 6 NADH
  • 2 FADH2
  • 2 ATP

Importance of B Vitamins

• Essential for enzyme reactions and cofactors in the Krebs cycle.

Amino Acids and Fatty Acids

• Amino acids can both enter and exit the Krebs cycle.
• Fatty acids can feed into or be produced from Acetyl CoA.

Ketogenesis

• Occurs when there is no glucose.
• Oxaloacetate is used to generate glucose, leading to acetyl CoA accumulation.
• Accumulated acetyl CoA turns into ketones, which the brain can use for energy.

Conclusion

• Overview of the Krebs cycle and its crucial role in energy production.
• Mention of further resources and information available on social media.