Glycolysis: In-Depth Notes

Chapter 16: Glycolysis Overview

  • Glycolysis converts glucose to pyruvate, generating ATP and NADH.
16.1 Glycolysis as an Energy-Conversion Pathway
  • ATP Generation: Glycolysis yields a net gain of 2 ATP from one glucose molecule.
  • Enzyme Organization: Enzymes in glycolysis are organized into complexes for efficiency.
Phases of Glycolysis

  1. Investment Phase (Steps 1-5):

    • Glucose is trapped and modified; cleaved into two 3-carbon compounds.
    • Key Enzymatic Steps:
      • Step 1: Glucose phosphorylated to glucose 6-phosphate via hexokinase, consuming ATP.
      • Step 2: Phosphoglucose isomerase converts glucose 6-phosphate to fructose 6-phosphate.
      • Step 3: Phosphofructokinase (PFK) adds a phosphate to form fructose 1,6-bisphosphate.
      • Step 4: Aldolase cleaves fructose 1,6-bisphosphate into dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (GAP).
      • Step 5: Triose phosphate isomerase interconverts GAP and DHAP.

  2. Yield Phase (Steps 6-10):

    • Oxidation of 3-carbon compounds to pyruvate with ATP generation.
    • Key Enzymatic Steps:
      • Step 6: GAP is oxidized to 1,3-bisphosphoglycerate, producing NADH via glyceraldehyde 3-phosphate dehydrogenase.
      • Step 7: Phosphoglycerate kinase transfers a phosphate to ADP, producing ATP.
      • Steps 8-10: Conversion of 3-phosphoglycerate to pyruvate, generating additional ATP (phosphoenolpyruvate to pyruvate catalyzed by pyruvate kinase).
Overall Reaction of Glycolysis
  • Converts 1 glucose molecule into 2 pyruvate, a net of 2 ATP and 2 NADH.
Regulation of Glycolysis
  • Irreversible Steps:
    • Key control points are catalyzed by hexokinase, PFK, and pyruvate kinase.
  • Muscle Regulation:
    • Energy charge influences regulation; inhibited by ATP and stimulated by AMP and fructose 1,6-bisphosphate.
  • Liver Regulation:
    • Maintains blood glucose levels; regulated by glucokinase (high Km for glucose), ATP, citrate, and fructose 2,6-bisphosphate.
16.2 NAD+ Regeneration
  • Important for continuous ATP production during glycolysis.
  • Fermentation Processes:
    • Alcoholic fermentation produces ethanol, regenerating NAD+.
    • Lactic acid fermentation converts pyruvate to lactate, also regenerating NAD+.
16.3 Metabolism of Fructose and Galactose
  • Fructose Pathway:
    • Metabolized by fructokinase or the fructose 1-phosphate pathway in the liver, bypassing PFK, potentially leading to obesity and metabolic issues.
16.4 Glycolytic Pathway Control
  • Glycolysis is tightly controlled to match energy needs and maintain homeostasis across different tissue types (muscle vs. liver).
16.5 Glycolysis and Insulin Release
  • Pancreatic β cells sense glucose and secrete insulin based on glycolysis-generated ATP levels.
Key Enzymes of Glycolysis:
  • Hexokinase
  • Phosphoglucose isomerase
  • Phosphofructokinase (PFK)
  • Aldolase
  • Triose phosphate isomerase
  • Glyceraldehyde 3-phosphate dehydrogenase
  • Phosphoglycerate kinase
  • Phosphoglycerate mutase
  • Enolase
  • Pyruvate kinase
Quick Quiz
  • What is the rate-limiting step of glycolysis?