lecture 4 114b

Overview of Glycolysis

  • Glycolysis consists of two halves: the energy investment phase and the energy payoff phase.
  • The net equation: 1 glucose → 2 pyruvate, 2 NADH, 2 ATP.

First Half of Glycolysis Recap

  • Step 1: Glucose (6C) is phosphorylated using ATP to become Glucose-6-phosphate.
  • Step 2: Isomerization converts Glucose-6-phosphate to Fructose-6-phosphate.
  • Step 3: Fructose-6-phosphate is phosphorylated to Fructose-1,6-bisphosphate, consuming a second ATP.
  • Step 4: Cleavage of Fructose-1,6-bisphosphate yields two 3C sugars: Dihydroxyacetone phosphate (DHAP) and Glyceraldehyde-3-phosphate (GAP), with only GAP proceeding through glycolysis.

Second Half of Glycolysis

  • Step 5: Conversion of DHAP to GAP
    • Enzyme: Triose phosphate isomerase.
  • Step 6: GAP Dehydrogenation
    • Enzyme: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).
    • NAD⁺ is reduced to NADH, forming 1,3-bisphosphoglycerate (1,3-BPG).
  • Step 7: ATP Formation
    • Enzyme: Phosphoglycerate kinase.
    • ATP generated by transferring a phosphate from 1,3-BPG to ADP.
  • Step 8: Isomerization
    • Enzyme: Phosphoglycerate mutase.
    • The phosphate moves from carbon 3 to carbon 2.
  • Step 9: Formation of another High Energy Compound
    • Enzyme: Enolase.
    • Produces phosphoenolpyruvate (PEP).
  • Step 10: Final ATP Production
    • Enzyme: Pyruvate kinase.
    • PEP is converted to pyruvate, producing ATP.

Energy Changes

  • Overall, glycolysis yields: 2 ATP (net gain), 2 NADH, 2 pyruvate.
  • ATP is produced via substrate-level phosphorylation.
  • Reversible reactions like those involving ATP hydrolysis depend on the concentrations of reactants and products.

Regulation of Glycolysis

  • Key regulated steps include:
    1. Hexokinase (step 1)
    2. Phosphofructokinase (step 3, main regulatory step)
    3. Pyruvate kinase (step 10)
  • Phosphofructokinase is activated by ADP, AMP and inhibited by ATP, making it a key sensor of energy status in the cell.

Fermentation Pathways

  • Under anaerobic conditions, pyruvate can be converted to lactate in muscles (lactic acid fermentation).
  • Alternatively, it may be converted to ethanol in yeast processes, involving:
    1. Decarboxylation to release CO₂ (enzyme: pyruvate decarboxylase).
    2. Alcohol dehydrogenase converts acetaldehyde to ethanol while regenerating NAD⁺.

Pentose Phosphate Pathway

  • An alternative pathway for glucose-6-phosphate; produces NADPH and ribose.
  • NADPH is crucial for biosynthetic pathways; ribose is essential for nucleic acid synthesis.
  • The pathway operates by taking glucose-6-phosphate and converting it into ribulose-5-phosphate while capturing reducing equivalents as NADPH.

Key Takeaways

  • Glycolysis is an essential metabolic pathway that provides energy quickly.
  • Regulation and/or coupling of pathways ensures cellular energy needs are met efficiently, adapting to varying physiological conditions.