Glycolysis Lecture Notes

Key Concepts

What is Glycolysis?

• Oxidation of glucose, a 6-carbon monosaccharide, into two 3-carbon pyruvate molecules through 10 steps.

Glucose Entry into Cells

• Glucose: 6-carbon water-soluble molecule.
• Transporter: Glucose can't diffuse through cell membranes; it requires GLUT transporters (bi-directional).

Types of GLUT Transporters

• Mnemonic: BBBKIPS Pink Mother Father
  • GLUT1: Blood (Red Blood Cells), Baby (Fetus), Blood-Brain Barrier
  • GLUT2: Kidney, Liver, Pancreas, Gastrointestinal Tract
  • GLUT3: Placenta, Neurons, Kidney
  • GLUT4: Muscle, Fat (Adipose); Insulin Dependent

Initial Steps

1. Glucose phosphorylation (traps glucose in the cell by making it glucose 6-phosphate)

   • Enzymes: Hexokinase (muscle, tissues), Glucokinase (liver)
   • Uses 1 ATP

2. Isomerization of glucose 6-phosphate to fructose 6-phosphate

   • Enzyme: Phosphohexose isomerase

3. Phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate (committed step)

   • Enzyme: Phosphofructokinase 1 (PFK1)
   • Uses 1 ATP

Splitting and Conversion Steps

4. Cleavage of fructose 1,6-bisphosphate into two 3-carbon molecules: dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (GA3P)

   • Enzyme: Aldolase
   • DHAP is converted to GA3P
   • Enzyme: Triose phosphate isomerase

5. Oxidation and Phosphorylation of GA3P to 1,3-bisphosphoglycerate

   • Enzyme: Glyceraldehyde 3-phosphate dehydrogenase
   • Generates 2 NADH (one for each GA3P)
   • Adds an inorganic phosphate (Pi)

6. Substrate-Level Phosphorylation of 1,3-bisphosphoglycerate to 3-phosphoglycerate

   • Enzyme: Phosphoglycerate kinase
   • Produces 2 ATP (one for each GA3P)

Final Steps

7. Mutation of 3-phosphoglycerate to 2-phosphoglycerate

   • Enzyme: Phosphoglycerate mutase

8. Formation of Phosphoenolpyruvate (PEP) from 2-phosphoglycerate

   • Enzyme: Enolase

9. Substrate-Level Phosphorylation of PEP to pyruvate

   • Enzyme: Pyruvate kinase
   • Produces 2 ATP (one for each PEP)

Fate of Pyruvate

• Under anaerobic conditions: Converted to lactic acid via lactate dehydrogenase
  • NADH is oxidized to NAD+
  • Lactic acid can lead to reduced blood pH
• Under aerobic conditions: Converted to acetyl CoA for the Citric Acid Cycle
• Clinical relevance of high lactate dehydrogenase: Indicates anaerobic metabolism, possible ischemia or other oxygen-deprivation conditions.

Summary

• Glycolysis occurs in the cytoplasm.
• Starting substrate: Glucose
• End product: 2 Pyruvate
• Net ATP production: 2 ATP
• NADH production: 2 NADH
• Anaerobic process: Can lead to lactic acid formation

Important Enzymes & Terms

• Hexokinase/Glucokinase: Phosphorylates glucose (Uses ATP)
• Phosphohexose isomerase: Isomerizes glucose 6-phosphate to fructose 6-phosphate
• Phosphofructokinase 1 (PFK1): Phosphorylates fructose 6-phosphate (Uses ATP)
• Aldolase: Cleaves fructose 1,6-bisphosphate into DHAP and GA3P
• Triose phosphate isomerase: Converts DHAP to GA3P
• Glyceraldehyde 3-phosphate dehydrogenase: Converts GA3P to 1,3-bisphosphoglycerate, produces NADH
• Phosphoglycerate kinase: Converts 1,3-bisphosphoglycerate to 3-phosphoglycerate, produces ATP
• Phosphoglycerate mutase: Converts 3-phosphoglycerate to 2-phosphoglycerate
• Enolase: Converts 2-phosphoglycerate to phosphoenolpyruvate (PEP)
• Pyruvate kinase: Converts PEP to pyruvate, produces ATP
• Lactate dehydrogenase: Converts pyruvate to lactic acid under anaerobic conditions

Next video topic: Transition Step - Conversion of pyruvate to acetyl CoA for the Citric Acid Cycle.