Glycolysis Lecture Notes

Overview

• Glycolysis is a biochemical pathway for ATP generation.
• Involves spontaneous and non-spontaneous steps, with regulatory mechanisms.

Importance of Glucose

• Universally used by organisms as a primary fuel.
• Red Blood Cells (RBCs) and the brain primarily rely on glucose.
• Reasons for Glucose Preference:
  • Stable hexose with low non-enzymatic glycosylation tendency.
  • Primitive fuel source due to its stability and availability.

End Products of Glycolysis

• Starts with 1 glucose (6 carbons) and produces:
  • 2 Pyruvate molecules
  • 2 ATP molecules
  • 2 NADH molecules

Stages of Glycolysis

Stage 1: Energy Investing

• Involves consuming ATP to prepare glucose for energy extraction.
• Steps and Enzymes:
  1. Glucose to Glucose 6-phosphate
     • Enzyme: Transferase (hexokinase)
  2. Glucose 6-phosphate to Fructose 6-phosphate
     • Enzyme: Isomerase
  3. Fructose 6-phosphate to Fructose 1,6-bisphosphate
     • Enzyme: Transferase (phosphofructokinase)
  4. Fructose 1,6-bisphosphate to Glyceraldehyde-3-phosphate (G3P) & Dihydroxyacetone phosphate
     • Enzyme: Lyase (aldolase)
  5. Dihydroxyacetone phosphate to Glyceraldehyde-3-phosphate
     • Enzyme: Isomerase

Stage 2: Energy Producing

• Involves producing ATP and NADH.
• Steps and Enzymes:
  1. Glyceraldehyde-3-phosphate to 1,3-Bisphosphoglycerate
     • Enzyme: Dehydrogenase (oxido-reductase)
  2. 1,3-Bisphosphoglycerate to 3-Phosphoglycerate
     • Enzyme: Transferase (substrate-level phosphorylation)
  3. 3-Phosphoglycerate to 2-Phosphoglycerate
     • Enzyme: Isomerase
  4. 2-Phosphoglycerate to Phosphoenolpyruvate
     • Enzyme: Lyase
  5. Phosphoenolpyruvate to Pyruvate
     • Enzyme: Transferase (substrate-level phosphorylation)

Regulatory Steps & Enzymes

• Hexokinase: Traps glucose in the cell.
• Phosphofructokinase (PFK): Adds a second phosphate, making the molecule symmetric.
• Rate-limiting steps are often highly regulated.

Energetics

• Net production of 2 ATP from glycolysis.
• Delta G Values: Indicate irreversible steps (highly spontaneous).

NADH and Regeneration of NAD+

• NADH needs to be oxidized back to NAD+ for glycolysis to continue.
• Methods of Regeneration:
  • Further oxidation in the Krebs cycle.
  • Ethanol fermentation or lactic acid fermentation.

Fermentation Pathways

Ethanol Fermentation

• Involves conversion of pyruvate to ethanol.
• Enzymes: Pyruvate decarboxylase and alcohol dehydrogenase.

Lactic Acid Fermentation

• Converts pyruvate to lactate.
• Enzyme: Lactate dehydrogenase.

Entry of Other Sugars

• Fructose and Galactose must be converted to glycolytic intermediates.
• Fructose Entry: Via fructose 6-phosphate or DHAP/GAAP (in liver).
• Galactose Entry: Converted to glucose 6-phosphate.
• Metabolic Impact of Fructose: Can bypass regulatory glycolysis steps leading to metabolic syndromes like obesity.

Conclusion

• Glycolysis is a crucial pathway for ATP production and metabolic intermediate synthesis.
• Understanding its regulation and integration with other pathways is key to metabolic health.