Glycolysis Lecture Notes

Introduction to Glycolysis

• Glycolysis is the process of oxidizing glucose (a 6-carbon monosaccharide) into pyruvate (two 3-carbon molecules).
• Glucose is water-soluble and requires specialized transporters to enter the cell.

Glucose Transporters (GLUT)

• GLUT Transporters: Specialized proteins that transport glucose across the cell membrane. They are bidirectional, allowing glucose movement both into and out of the cell.
• Types of GLUT Transporters:
  • GLUT1: Found in red blood cells, fetus, and blood-brain barrier.
  • GLUT2: Present in kidneys, liver, pancreas, and some parts of the gastrointestinal tract.
  • GLUT3: Located in the placenta, neurons, and kidneys.
  • GLUT4: Insulin-dependent, found in muscle and adipose tissues.

Glycolysis Steps

Step 1: Glucose to Glucose-6-Phosphate

• Glucose enters the cell and is phosphorylated to glucose-6-phosphate.
• Enzymes: Hexokinase (in muscles and various tissues) and Glucokinase (in the liver).
• Energy: Consumes 1 ATP (converts ATP to ADP).

Step 2: Glucose-6-Phosphate to Fructose-6-Phosphate

• Isomerization of glucose-6-phosphate to fructose-6-phosphate.
• Enzyme: Phosphohexose isomerase.

Step 3: Fructose-6-Phosphate to Fructose-1,6-Bisphosphate

• Enzyme: Phosphofructokinase-1 (PFK-1).
• Energy: Consumes 1 ATP.

Steps 4 & 5: Fructose-1,6-Bisphosphate Cleavage

• Splits into dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P).
• Enzyme: Aldolase; DHAP is converted to G3P by triose phosphate isomerase.

Step 6: G3P to 1,3-Bisphosphoglycerate

• Enzyme: Glyceraldehyde-3-phosphate dehydrogenase.
• Produces 2 NADH from NAD+.
• Adds inorganic phosphate.

Step 7: 1,3-Bisphosphoglycerate to 3-Phosphoglycerate

• Enzyme: Phosphoglycerate kinase.
• Produces 2 ATP.

Step 8: 3-Phosphoglycerate to 2-Phosphoglycerate

• Enzyme: Phosphoglycerate mutase.

Step 9: 2-Phosphoglycerate to Phosphoenolpyruvate (PEP)

• Enzyme: Enolase.

Step 10: PEP to Pyruvate

• Enzyme: Pyruvate kinase.
• Produces 2 ATP.

Fate of Pyruvate

• Anaerobic Conditions: Pyruvate is converted into lactic acid by lactate dehydrogenase, regenerating NAD+.
• Aerobic Conditions: Pyruvate is converted into Acetyl-CoA for the Krebs cycle (discussed in next lecture).

Glycolysis Summary

• Location: Cytoplasm.
• Starting Substrate: Glucose.
• End Products: 2 pyruvate molecules.
• Net ATP Yield: 2 ATP (gross 4 ATP, 2 used).
• Byproducts: 2 NADH.
• Anaerobic Process: Can lead to lactic acid production under low oxygen conditions.

Clinical Relevance

• High lactate dehydrogenase levels can indicate tissue hypoxia or other medical conditions (e.g., myocardial infarction, ischemia).

Next Topics

• Transition from pyruvate to Acetyl-CoA (aerobic conditions).

Note: This lecture provided an in-depth step-by-step breakdown of the glycolytic pathway, emphasizing the enzymes involved, energy consumption, and production, as well as the regulatory aspects of glycolysis. The clinical implications of glycolysis in relation to tissue oxygenation were also discussed.