Glycolysis Study Notes

Glycolysis Study Notes

Overview of Metabolism

  • Metabolism: A series of interconnected chemical reactions occurring within a cell.
      - Metabolites: The chemical compounds involved in metabolism.
      - Pathways: Enzymatic reactions organized into discrete pathways, proceeding stepwise to transform substrates into end products through specific chemical intermediates.

Glycolysis

  • Definition: Glycolysis (from Greek: glykys "sweet" and lysis "splitting") is a metabolic process involving the degradation of glucose into two molecules of pyruvate through a series of enzyme-catalyzed reactions.
      - Presence of Oxygen: Occurs in the presence of oxygen and conserves energy in the form of ATP and NADH.
      - Anaerobic Conversion: Pyruvate can be further processed to lactate anaerobically.
      - Alternative Naming: Also referred to as the Embden-Meyerhof pathway.
Characteristics of Glycolysis
  • Unique Pathway: It functions both aerobically (with oxygen) and anaerobically (without oxygen).
  • Major Pathway: Serves as a primary pathway for glucose utilization in virtually all cells across prokaryotic and eukaryotic organisms.
      - Location in Eukaryotic Cells: Cytosol.
Types of Metabolic Pathways
  1. Linear Pathways: Example - Glycolysis.
  2. Cyclic Pathways: Example - Citric acid cycle.
  3. Spiral Pathways: Example - Biosynthesis of Fatty Acids.
Functions of Metabolic Pathways
  • Generate energy to drive vital functions.
  • Synthesize biological molecules.

Catabolic vs. Anabolic Pathways

  • Catabolic Pathways:
      - Involved in oxidative breakdown of larger complexes.
      - Usually exergonic (release energy).
  • Anabolic Pathways:
      - Synthesize compounds.
      - Usually endergonic (consume energy).

Characteristics of Metabolism

  1. Metabolic pathways are irreversible.
  2. Every metabolic pathway has a committed first step.
  3. All metabolic pathways are regulated.
  4. Metabolic pathways in eukaryotic cells occur in specific cellular locations.

Phases of Glycolysis

  • Glycolysis leads to the breakdown of 6-carbon glucose into two molecules of 3-carbon pyruvate, divided into two phases:
      1. Phase 1: Preparatory Phase (Energy-requiring).
      2. Phase 2: Payoff Phase (Energy-generating).
Preparatory Phase
  • Overview: Consists of the first 5 steps, involving the phosphorylation of glucose by ATP to yield fructose-1,6-biphosphate, which is then split into two 3-carbon molecules (Glyceraldehyde-3-phosphate).
      - ATP Investment: Requires the consumption of 2 ATP molecules to activate glucose for cleavage.
Payoff Phase
  • Overview: Last 5 reactions of glycolysis, marking the release of ATP molecules through the conversion of Glyceraldehyde-3-phosphate to pyruvate.
      - ATP Generation: 4 moles of ADP are phosphorylated to ATP; the net yield is 2 moles of ATP per mole of glucose due to the ATP utilized in Phase 1.

Stepwise Explanation of Glycolysis

  1. Step 1: Phosphorylation
       - Reaction: Glucose is phosphorylated by ATP to form glucose-6-phosphate.
       - Enzyme: Hexokinase (irreversible reaction).
  2. Step 2: Isomerization
       - Reaction: Rearrangement of glucose-6-phosphate to fructose-6-phosphate.
       - Enzyme: Phosphoglucoisomerase (reversible reaction).
  3. Step 3: Phosphorylation
       - Reaction: Fructose-6-phosphate is phosphorylated to fructose-1,6-bisphosphate.
       - Enzyme: Phosphofructokinase (irreversible reaction).
  4. Step 4: Breakdown
       - Reaction: Cleavage of fructose-1,6-bisphosphate to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.
       - Enzyme: Aldolase.
  5. Step 5: Isomerization
       - Reaction: Dihydroxyacetone phosphate is converted to glyceraldehyde-3-phosphate.
       - Enzyme: Triose phosphate isomerase.
  6. Step 6: Oxidation
       - Reaction: Two molecules of glyceraldehyde-3-phosphate are oxidized to form 1,3-bisphosphoglycerate.
       - Enzyme: Glyceraldehyde-3-phosphate dehydrogenase.
  7. Step 7: First Substrate Level Phosphorylation
       - Reaction: Transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP, forming ATP and 3-phosphoglycerate.
       - Enzyme: Phosphoglycerate kinase.
  8. Step 8: Rearrangement
       - Reaction: 3-phosphoglycerate is converted to 2-phosphoglycerate.
       - Enzyme: Phosphoglycerate mutase.
  9. Step 9: Dehydration
       - Reaction: Conversion of 2-phosphoglycerate to phosphoenolpyruvate via dehydration.
       - Enzyme: Enolase.
  10. Step 10: Second Substrate Level Phosphorylation
        - Reaction: Transfer of phosphate from phosphoenolpyruvate to ADP, creating ATP and pyruvate.
        - Enzyme: Pyruvate kinase (irreversible reaction).

Overall Balance Sheet of Glycolysis

  • Inputs:
      - Glucose + 2 ATP + 2 Pi + 2 NAD+ + 2 H+ + 4 ADP
  • Outputs:
      - 2 Pyruvate + 2 NADH + 2 ATP + 2 H+ + 2 H2O
  • Net Equation:
    extGlucose+2extPi+2extADP+2extNAD+→2extPyruvate+2extNADH+2extATP+2extH++2extH2extOext{Glucose} + 2 ext{Pi} + 2 ext{ADP} + 2 ext{NAD}^+ \rightarrow 2 ext{Pyruvate} + 2 ext{NADH} + 2 ext{ATP} + 2 ext{H}^+ + 2 ext{H}_2 ext{O}

Energy Yield in Glycolysis

  • ATP Consumption and Gain:
      - Step 1: Glucose to glucose-6-phosphate: 1 ATP consumed.
      - Step 3: Fructose-6-phosphate to fructose-1,6-bisphosphate: 1 ATP consumed.
      - Step 7: 1,3-diphosphoglycerate to 3-phosphoglycerate: 1 ATP gained (substrate-level phosphorylation).
      - Step 10: Phosphoenolpyruvate to pyruvate: 1 ATP gained (substrate-level phosphorylation).
  • Net Gain of ATP:
    extNetgain=4(extgained)−2(extconsumed)=2extATPext{Net gain} = 4 ( ext{gained}) - 2 ( ext{consumed}) = 2 ext{ ATP}

Conclusion

  • During glycolysis:
      - Glucose is oxidized to pyruvate.
      - NAD+ is reduced to NADH.
      - ADP is phosphorylated to ATP.