Glycolysis Lecture Notes

Introduction to Glycolysis

• Definition: Glycolysis is the process of splitting a glucose molecule (a 6-carbon sugar) into two pyruvate molecules (each with 3 carbons).
• Energy Production: During glycolysis, energy is released and captured as ATP and NADH. It is an energy-producing process.

Location and Net Reaction

• Location: Takes place in the cytosol of cells.
• Net Reaction:
  • Reactants: Glucose, 2 NAD+, 2 ADP, and 2 inorganic phosphate ions.
  • Products: 2 pyruvate, 2 NADH, 2 H+, 2 ATP, and 2 water molecules.
• Reduction Process: NAD+ is reduced to NADH by gaining a hydrogen.

Phases of Glycolysis

• Investment Phase (Steps 1-5):
  • Consumes energy (endothermic).
  • Requires 2 ATP molecules.
• Payoff Phase (Steps 6-10):
  • Produces more energy than consumed.
  • Yields 4 ATP molecules and 2 NADH, resulting in a net gain of 2 ATP and 2 NADH.

Steps of Glycolysis

Step 1: Phosphorylation of Glucose

• Input: Glucose, ATP.
• Output: Glucose 6-phosphate (G6P) and ADP.
• Enzyme: Hexokinase (requires Mg2+ as a cofactor).
• Irreversible: High negative delta G (-16.7 kJ/mol).

Step 2: Isomerization

• Input: Glucose 6-phosphate.
• Output: Fructose 6-phosphate (F6P).
• Enzyme: Phosphohexose isomerase (requires Mg2+).
• Reversible: Positive delta G (1.7 kJ/mol).

Step 3: Second Phosphorylation

• Input: Fructose 6-phosphate, ATP.
• Output: Fructose 1,6-bisphosphate (F1,6BP) and ADP.
• Enzyme: Phosphofructokinase-1 (PFK1).
• Irreversible: Negative delta G (-14.2 kJ/mol).

Step 4: Cleavage

• Input: Fructose 1,6-bisphosphate.
• Output: Glyceraldehyde 3-phosphate (G3P) and Dihydroxyacetone phosphate (DHAP).
• Enzyme: Aldolase.
• Reversible: Positive delta G (23.8 kJ/mol).

Step 5: Isomerization

• Input: DHAP.
• Output: G3P.
• Enzyme: Triose phosphate isomerase.
• Reversible: Converts DHAP to G3P, leading to two G3P molecules entering the payoff phase.

Step 6: Oxidation and Phosphorylation

• Input: G3P, NAD+, inorganic phosphate.
• Output: 1,3-bisphosphoglycerate (1,3-BPG), NADH, H+.
• Enzyme: Glyceraldehyde 3-phosphate dehydrogenase.
• Reversible: Oxidized G3P; NAD+ is reduced to NADH.

Step 7: Substrate-Level Phosphorylation

• Input: 1,3-BPG, ADP.
• Output: 3-phosphoglycerate (3-PG), ATP.
• Enzyme: Phosphoglycerate kinase.
• Reversible: Produces 2 ATP molecules.

Step 8: Mutase Reaction

• Input: 3-PG.
• Output: 2-phosphoglycerate (2-PG).
• Enzyme: Phosphoglycerate mutase.
• Reversible: Moves phosphate from C-3 to C-2.

Step 9: Dehydration

• Input: 2-PG.
• Output: Phosphoenolpyruvate (PEP), water.
• Enzyme: Enolase.
• Reversible: Water removal (dehydration).

Step 10: Final Phosphorylation

• Input: PEP, ADP.
• Output: Pyruvate, ATP.
• Enzyme: Pyruvate kinase.
• Irreversible: Produces 2 ATP, completing glycolysis.
• Cofactors: Requires Mg2+ and K+.

Summary

• Irreversible Steps: 1, 3, 10.
• Net Gain: 2 ATP, 2 NADH.
• Glycolysis is an essential energy-producing pathway in cellular metabolism, leading to the formation of pyruvate and high-energy molecules (ATP, NADH).