Thermodynamics
  • Review premed reaction basics
  • PEP Carboxykinase of gluconeogenesis is driven by both GTP hydrolysis and decarboxylation.
  • Lactate DH favors formation of lactate (negative ΔG), but mass action (lots of lactate, little pyruvate) pushes it to form pyruvate in the liver.
  • Free energy = energy available to do work = ΔG
  • Chemical equilibria = forward reaction occuring, and at the same time reverse reaction is also occuring.
    • Reaction moves forward if forward reaction is faster than reverse reaction.
    • Reaction moves backward if reverse reaction is faster than forward reaction.
    • System at equilibrium if forward reaction is occuring at the same rate as the reverse reaction.
    • System at equilibrium when ΔG = 0.
  • Group transfer potential
    • Group transfer = nucleophilic substitution.
    • Biological group transfers:
      • Acyl group: R-(C=O)-X
      • Phosphoryl group:R-O-PO32-
      • Glycosyl group: R-O-Sugar (review premed mechanism of this rxn)
    • Group transfer potential = ΔG for hydrolysis of that group. The more negative the ΔG for hydrolysis of the transfer group, the easier it is to transfer this group to another nucleophile.
  • ATP and other high energy compounds
    • Hydrolysis of phosphoanhydride bonds by itself requires energy. However, charge-charge repulsion and competing resonance structures
    • ATP → ADP + Pi (ΔG° = -30.5 kJ/mol)
    • ATP → AMP + PPi (ΔG° = -32.2 kJ/mol)
    • Phosphocreatine → creatine + Pi (ΔG° = -43.1 kJ/mol)
    • Phosphocreatine + ADP → creatine + ATP (ΔG° = -43.1 + 30.5 = -12.6 kJ/mol)
    • ΔG must be negative for reaction to be spontaneous.
    • High energy compounds = ΔG of hydrolysis very negative (ATP and anything with ΔG around or more negative than ATP)
    • Low energy compounds = ΔG of hydrolysis not as negative as ATP.
    • Higher energy compounds can drive the creation of lower energy compounds.
  • Glycogen metabolism
    • 1-4 bond easier to hydrolyze than 1-6 bond.
    • Glycogen breakdown by glycogen phosphorylase is favorable.
    • Debranching is unfavorable (involves breaking 1-6 and forming 1-4).
    • Glycogen synthesis by glycogen synthase is unfavorable (needs UTP).
    • Branching is favorable (involves breaking 1-4 and forming 1-6).
    • G1P → glycogen + Pi is thermodynamically unfavorable (+ΔG), which is why UDP-Glucose is used.
    • G1P + UTP → UDPG + PP has ΔG ~0
    • PPi → 2Pi is favorable because it has negative ΔG