Lecture Notes: NADH Utilization in Mitochondria

Overview

• Discussing NADH from glycolysis integration into the electron transport chain (ETC).
• Recap on NADH from Krebs cycle and transition step pushing protons into intermembrane space.

NADH from Glycolysis

1. Formation of Malate:

   • NADH generated from glycolysis converts to NAD+ via oxaloacetate (OAA).
   • OAA is converted to malate through the enzyme malate dehydrogenase.
   • Malate can cross mitochondrial membrane; OAA cannot.

2. Transport into Mitochondrial Matrix:

   • Malate enters the mitochondrial matrix via a specific transporter.
   • Inside, malate is converted back to OAA, generating NADH (an important step for the ETC).

3. Reconversion Process:

   • Enzyme involved: malate dehydrogenase.
   • OAA now needs to exit the mitochondria:
     • Combines with glutamate (an amino acid).
     • Forms aspartate and alpha-ketoglutarate (another Krebs cycle component).
   • Aspartate can exit the mitochondria, while alpha-ketoglutarate is reintroduced into the cycle.

The Malate-Aspartate Shuttle

• Process Summary:
  • NADH from cytosol converted to malate for transport.
  • Once inside, malate converts back to OAA, generating NADH for the ETC.
  • OAA combines with glutamate to produce aspartate which exits the mitochondria.

Other Mechanisms for NADH Transfer

Glycerol 3-Phosphate Shuttle

• Step 1:
  • Dihydroxyacetone phosphate (DHAP) converts to glycerol 3-phosphate when NADH donates electrons.
• Step 2:
  • Glycerol 3-phosphate enters mitochondria.
  • Converted back to DHAP while generating FADH2 (which enters the ETC).

Beta-Oxidation of Fatty Acids

• Fatty acids also involve CoA for transportation into mitochondria.
• Process:
  • CoA derivatives undergo oxidation via acyl-CoA dehydrogenase, generating FADH2.
  • Products re-enter ETC as FADH2.

Key Points

• NADH cannot cross mitochondrial membrane directly. Must be converted into malate or glycerol 3-phosphate to facilitate transport.
• Importance of oxygen:
  • Without oxygen, NADH unloads onto pyruvate, producing lactic acid.
  • The processes described only operate under aerobic conditions.

Conclusion

• The lecture covered how NADH from glycolysis can enter the mitochondrial electron transport chain through different mechanisms:
  1. Malate-aspartate shuttle.
  2. Glycerol 3-phosphate shuttle.
  3. Beta-oxidation of fatty acids.
• Next topic: ATP synthesis via oxidative phosphorylation.