Glycolysis Overview

Glycolysis

• Glycolysis is the breakdown of glucose to produce pyruvate and energy in the form of ATP
• Glucose is a key fuel source for the body
• Glucose can be stored in polymeric form as glycogen
• Glucose can be synthesized via Gluconeogenesis (a separate topic)
• Glycolysis occurs in the cytoplasm of the cell
• Glucose enters the cell via GLUT transporters, each with specific tissue expression:
  • GLUT1: red blood cells, blood-brain barrier, placenta
  • GLUT2: liver, pancreatic islets, small intestine, kidney
  • GLUT3: brain (neurons), testes
  • GLUT4: skeletal and heart muscle, fat
• Glycolysis is divided into two phases: preparatory and payoff phases

Preparatory phase (Steps 1-5)

• Preparatory phase requires ATP input
• Step 1: Glucose is phosphorylated to Glucose-6-phosphate (irreversible)
  • Requires enzyme Hexokinase (four isozymes encoded by different genes):
    • Muscle: Hexokinase 1 and 2
    • Liver: Hexokinase 4 (also known as Glucokinase)
• Step 2: Glucose-6-phosphate is isomerized to Fructose-6-phosphate (reversible)
  • Requires enzyme Phosphohexose Isomerase
• Step 3: Fructose-6-phosphate is phosphorylated to Fructose-1,6-Bisphosphate
  • Requires enzyme Phosphofructokinase-1 (PFK-1)
  • PFK-1 is allosterically regulated by ATP and AMP levels:
    • High ATP: PFK-1 is inhibited
    • Low ATP: PFK-1 is activated
• Step 4: Fructose-1,6-bisphosphate is split into two 3-carbon sugars:
  • Dihydroxyacetone phosphate (DHAP) and Glyceraldehyde-3-phosphate
  • Requires enzyme Aldolase
• Step 5: Dihydroxyacetone phosphate (DHAP) is converted to Glyceraldehyde-3-phosphate (reversible)
  • Requires enzyme Triose Phosphate Isomerase
  • Glyceraldehyde-3-phosphate is the only sugar that can continue through glycolysis

Payoff Phase (Steps 6-10)

• Payoff phase produces NADH and ATP
• Step 6: Glyceraldehyde-3-phosphate is oxidized to 1,3-Bisphosphoglycerate
  • Requires enzyme Glyceraldehyde-3-Phosphate Dehydrogenase
  • NAD+ is reduced to NADH
• Step 7: 1,3-Bisphosphoglycerate is converted to 3-Phosphoglycerate (reversible)
  • Requires enzyme Phosphoglycerate Kinase
  • Phosphate group is transferred to ADP, producing 1 ATP
• Step 8: 3-Phosphoglycerate is converted to 2-Phosphoglycerate
• Step 9: 2-Phosphoglycerate is converted to Phosphoenolpyruvate (PEP) (dehydration reaction)
  • Requires enzyme Enolase
• Step 10: Phosphoenolpyruvate (PEP) is converted to Pyruvate (irreversible)
  • Requires enzyme Pyruvate Kinase
  • Phosphate group is transferred to ADP, producing 1 ATP

Glycolysis Summary and Products

• Investment in the preparatory phase: 2 ATP
• Production in the payoff phase: 2 pyruvate, 2 NADH, 4 ATP
• Net yield per 1 glucose molecule: 2 ATP and 2 NADH

Glycolysis in Aerobic or Anaerobic Conditions

• Aerobic Conditions: Pyruvate is oxidized to Acetyl-CoA and CO2
  • Acetyl-CoA enters the Citric Acid Cycle
  • NADH is re-oxidized to NAD+ by donating electrons to the electron transport chain (producing ATP)
• Anaerobic Conditions: NADH donates electrons to pyruvate, converting it to lactate
  • This reaction is catalyzed by lactate dehydrogenase
  • NADH is re-oxidized to NAD+, maintaining the supply of NAD+ for glycolysis to continue