Glycolysis Lecture Notes

Introduction to Glycolysis

• Definition: Glycolysis is the process of oxidizing glucose, a six-carbon monosaccharide (sugar), into pyruvate.
• Glucose originates from the diet and enters cells where it is processed.
• Glycolysis comprises about 10 steps, converting glucose into two molecules of pyruvate (each three-carbon molecules).

Glucose Transport to Cells

• Glucose
  • A six-carbon molecule, depicted as six circles.
  • Water-soluble, cannot diffuse passively through the cell membrane.
• GLUT Transporters
  • Specialized transporters moving glucose into and out of cells.
  • Bidirectional transport.
  • Types:
    • GLUT1: Blood (red blood cells), fetus (baby), blood-brain barrier.
    • GLUT2: Kidney, liver, pancreas.
    • GLUT3: Placenta, neurons, kidney.
    • GLUT4: Muscle, adipose tissue (fat), insulin-dependent.

Glycolysis Pathway Steps

1. Glucose to Glucose-6-Phosphate
   • Enzymes: Hexokinase (muscles) and glucokinase (liver).
   • Hexokinase is found in many tissues; glucokinase is liver-specific.
   • Phosphate group added from ATP, converting to ADP.
2. Glucose-6-Phosphate to Fructose-6-Phosphate
   • Enzyme: Phosphohexose isomerase.
   • Isomerization: Transition from an aldehyde to a ketone form.
3. Fructose-6-Phosphate to Fructose-1,6-bisphosphate
   • Enzyme: Phosphofructokinase-1 (PFK-1).
   • Irreversible step, ATP used to add a phosphate group.
4. Fructose-1,6-bisphosphate to Dihydroxyacetone Phosphate (DHAP) and Glyceraldehyde-3-Phosphate (G3P)
   • Enzyme: Aldolase.
   • DHAP is converted to G3P for glycolysis continuation via triose phosphate isomerase.
5. Glyceraldehyde-3-Phosphate to 1,3-Bisphosphoglycerate
   • Enzyme: Glyceraldehyde-3-phosphate dehydrogenase.
   • Produces 2 NADH by transferring hydrides and adds inorganic phosphate.
6. 1,3-Bisphosphoglycerate to 3-Phosphoglycerate
   • Enzyme: Phosphoglycerate kinase.
   • Produces 2 ATP by transferring phosphate to ADP.
7. 3-Phosphoglycerate to 2-Phosphoglycerate
   • Enzyme: Phosphoglycerate mutase.
8. 2-Phosphoglycerate to Phosphoenolpyruvate (PEP)
   • Enzyme: Enolase.
9. Phosphoenolpyruvate to Pyruvate
   • Enzyme: Pyruvate kinase.
   • Produces 2 ATP, irreversible step.

Fate of Pyruvate

• Anaerobic Conditions (low/no oxygen):
  • Pyruvate converted to lactic acid.
  • Enzyme: Lactate dehydrogenase, reversible.
  • Lactic acid implications: Decreases pH, linked to conditions like myocardial infarction, ischemia.
• Aerobic Conditions:
  • Conversion to acetyl-CoA (to be discussed in future lectures).

Summary of Glycolysis

• Occurs in the cytoplasm.
• Starting substrate: Glucose.
• End product: Two pyruvate molecules.
• Byproducts:
  • Gross 4 ATP generated, 2 ATP net gain.
  • 2 NADH produced.
• Typically an anaerobic process, producing lactic acid if no oxygen is present.

Conclusion

• The lecture covered glycolysis steps and their regulation.
• Transition to aerobic pathways and further pyruvate processing will be discussed in subsequent lectures.