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Understanding the Krebs Cycle and Its Implications

Apr 23, 2025

Biochemistry Lecture Notes: Krebs Cycle and Related Topics

Overview of the Lecture

  • Focus on understanding the Krebs cycle.
  • Importance of repetition and storytelling to memorize pathways (e.g., starting from phenylalanine or glucose).

Case Study

  • Patient Scenario: 52-year-old homeless male, suspected withdrawal seizures, elevated gamma-glutamyl transferase (GGT).
  • Key Point: Importance of knowing the Krebs cycle and its basics.
  • Important Enzymes: Pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase.
  • Cofactors Needed: Thiamine, lipoic acid, pantothenic acid, FAD, NAD.

Memorization Tips

  • Acronym: "Citrate is Krebs' Starting Substrate For Making Oxaloacetate."
    • Key steps to remember involve decarboxylation and energy production.
  • Key Steps:
    • Isocitrate to alpha-ketoglutarate (rate-limiting step): Influenced by NADH, ATP, ADP, and AMP.
    • Alpha-ketoglutarate step: Requires cofactors (thiamine, etc.).
    • Succinyl-CoA to succinate: Produces GTP.
    • Production of FADH2 for electron transport.

Alcohol Withdrawal and Biochemistry

  • Deficiencies: B1 (Thiamine) often deficient in alcoholics.
  • Associated Conditions: Wernicke-Korsakoff syndrome (confusion, ophthalmoplegia, ataxia).
  • Test Questions Insight: Often involve B1 as a cofactor for key steps.

Maple Syrup Urine Disease (MSUD)

  • Symptoms: Lethargic newborn with sweet odor in urine.
  • Deficiency: Alpha-keto acid dehydrogenase defective, affecting branched-chain amino acids (isoleucine, leucine, valine).
  • Dietary Restriction: Focus on restricting leucine.

Starvation and Krebs Cycle

  • Reaction: Conversion of pyruvate to phosphoenolpyruvate during starvation.
  • Source of Energy: GTP produced in the Krebs cycle.

Key Learnings

  • Krebs Cycle Steps: Understand and memorize key four steps for biochemistry questions.
  • Integration: Connect pathways from phenylalanine to glucose through the Krebs cycle.

Concluding Remarks

  • Study Strategy: Emphasize the narrative of pathways for effective memorization and application.
  • Important Points: Focus on rate-limiting steps, cofactor dependencies, and energy production aspects of the Krebs cycle.