Glycolysis Lecture Notes

Introduction

• Topic: Glycolysis (also known as the M. den Meyerhoff-Parnas pathway)
• Importance: Occurs in both aerobic and anaerobic conditions; crucial for energy production.

Important Aspects of Glycolysis

• Universal Occurrence: Happens in all body cells in the cytoplasm.
• Conditions: Operates both aerobically and anaerobically.
• Energy Source: Vital for mature RBCs (no mitochondria, relies solely on glycolysis).
• Exercise: Provides energy anaerobically during strenuous exercise when oxygen is low.
• Cardiac Muscles: Low glycolytic activity leads to poor prognosis in ischemic conditions.
• Biochemical Contributions: Generates carbon skeletons for non-essential amino acids and glycerol for fats.
• Gluconeogenesis: Involves reversible steps in glycolysis.

Steps in Glycolysis

1. Glucose to Glucose 6-Phosphate: Catalyzed by hexokinase/glucokinase (requires ATP, forms ADP).
2. Isomerization: Glucose 6-phosphate to fructose 6-phosphate.
3. Phosphorylation: Fructose 6-phosphate to fructose 1,6-bisphosphate.
4. Cleavage by Aldolase: Fructose 1,6-bisphosphate to DHAP and glyceraldehyde 3-phosphate.
5. Interconversion: DHAP to glyceraldehyde 3-phosphate.
6. Subsequent Steps: Glyceraldehyde 3-phosphate to 3-phosphoglycerate to 2-phosphoglycerate to phosphoenolpyruvate and finally to pyruvate.
7. Anaerobic Conditions: Pyruvate is converted into lactate.

Key Enzymes and Irreversible Steps

• Hexokinase/Glucokinase: First irreversible step.
• Phosphofructokinase: Second irreversible, rate-limiting, and committed step (determines pathway rate and commits glucose to glycolysis).
• Pyruvate Kinase: Third irreversible step.

Energetics

• Aerobic Conditions:
  • 7 ATPs produced (2 NADH yield 5 ATP + 2 substrate-level phosphorylations yielding 4 ATPs, minus 2 ATPs used initially).
• Anaerobic Conditions:
  • 2 ATPs produced (NADH used concurrently in lactate conversion).

Regulation

• Key Enzymes: Hexokinase/glucokinase, phosphofructokinase, and pyruvate kinase.
• Hexokinase: Inhibited by glucose 6-phosphate.
• Glucokinase: Regulated by insulin (activates) and glucagon (inhibits).
• Phosphofructokinase:
  • Activated by insulin, AMP, and fructose 2,6-bisphosphate.
  • Inhibited by ATP and citrate.
  • Inducible enzyme (induced by insulin, repressed by glucagon).
• Pyruvate Kinase: Activated by insulin, inhibited by glucagon via phosphorylation/dephosphorylation.

Summary

• The glycolytic pathway is crucial for energy production, especially under anaerobic conditions.
• It is regulated through key enzymes affected by hormones and allosteric factors.
• Understanding the steps, regulation, and energetics is essential for mastering carbohydrate metabolism.