In-Depth Notes on Metabolism II: Krebs Cycle and Electron Transport Chain

Overview of Metabolism II

• Focus on the Krebs Cycle and Electron Transport Chain.

Reminder from Last Lecture

• Catabolism Stages:
  • Stage 1: Digestion of food into small molecules (carbohydrates, fatty acids, amino acids).
  • Stage 2: Degradation of these small molecules into Acetyl CoA.
  • Stage 3: Oxidation of Acetyl CoA in the Citric Acid Cycle (Krebs Cycle) to produce CO2 and reduced coenzymes.
  • Stage 4: Oxidation of reduced coenzymes to release energy to synthesize ATP.

Glycolysis Recap

• Net result of glycolysis:
  ext{glucose} + 2 ext{NAD}^+ + 2 ext{(ADP + P)}
  ightarrow 2 ext{pyruvate} + 2 ext{NADH} + 2 ext{ATP}
• Conversion of pyruvate to Acetyl CoA is catalyzed by the pyruvate dehydrogenase (PDH) complex.

Coenzymes in Metabolism

• Coenzyme A (CoA): Synthesized from vitamin B5, plays a critical role in energy production by forming acetyl CoA.
• Oxidizing/Reducing Agents:
  • NAD+: Oxidizing agent; forms NADH.
  • FAD: Oxidizing agent; forms FADH2.
  • Example: Under anaerobic conditions, pyruvate is converted to lactate, producing NADH from NAD+.

Pyruvate Dehydrogenase (PDH)

• PDH is a large enzyme complex consisting of:
  • 8 trimers of E2 (24 active sites).
  • 24 E1 subunits.
  • 12 E3 enzymes.
• PDH is involved in regulating glucose metabolism and is influenced by factors like hypoxia-inducible factor-1 (HIF-1).

Citric Acid Cycle (Krebs Cycle)

• Overview:
  • An 8-step metabolic pathway converting acetyl CoA into CO2 and water, generating reduced coenzymes (NADH, FADH2).
• Phase 1 (Reactions 1-4):
  • Acetyl CoA (2 C’s) combines with oxaloacetate (4 C’s) to form citrate (6 C’s).
  • Two carbons released as CO2 yield two NADH.
• Phase 2 (Reactions 5-8):
  • Succinyl CoA is converted to succinate, producing GTP and later regenerating oxaloacetate to continue the cycle.
• Net Result of Citric Acid Cycle:
  ext{Acetyl CoA} + 3 ext{NAD}^+ + ext{FAD} + ext{GDP} + ext{Pi}
  ightarrow 2 ext{CO}2 + 3 ext{NADH} + ext{FADH}2 + ext{GTP}

Production of ATP from Glucose

• Total ATP yield from catabolism of one glucose molecule can be up to 32 ATP:
  • Glycolysis (2 ATP + 2 NADH)
  • Citric Acid Cycle (2 ATP from GTP + 6 NADH + 2 FADH2)
  • Electron Transport Chain (recycling reduced coenzymes)

Electron Transport Chain

• Overview:
  • Takes place in mitochondria; it is the final stage generating a majority of ATP.
  • Involves four enzyme complexes that facilitate oxidation/reduction reactions.
• Process: Starts with oxidation of NADH and FADH2, leading to the pumping of H+ ions and establishing electrochemical gradients for ATP synthesis via ATP synthase.

ATP Yield Calculation Example

• For 3.3 pounds of carbohydrates:
  • Calculate moles of glucose and respective ATP, GTP, NADH, FADH2 outputs using stoichiometry:
    $ext{1,743 g of carbs} / ext{180 g/mol} = 9.7 ext{ mol glucose}$
  • Results:
  • ATP: 19.4 mol
  • GTP: 19.4 mol
  • NADH: 97 mol
  • FADH2: 19.4 mol

Summary of Catabolism Steps

1. Step 1: Glycolysis
   • Glucose converted to 2 pyruvate molecules, producing 2 NADH and 2 ATP.
2. Step 2: Citric Acid Cycle
   • Acetyl CoA enters, producing 3 NADH, 1 FADH2, and 1 GTP.
3. Step 3: Electron Transport Chain
   • Utilizes reduced coenzymes to create ATP through proton gradient manipulation.