Question

Conversion of pyruvate to glucose by reversal of glycolysis has a ?Go’ of +84 kJ/mol, whereas gluconeogenesis occurs with a ?Go’ of ?38 kJ/mol. Where does the energy come from that drives gluconeogenesis? Show the three enzyme reactions where this energy is consumed.

Answer 1

gluconeogenesis is in essence glycolysis in reverse. And, of the ten reactions that constitute gluconeogenesis, seven are shared with glycolysis; these reactions have a ?G close to zero, therefore easily reversible. However, under intracellular conditions, the overall ?G of glycolysis is about -63 kJ/mol (-15 kcal/mol) and of gluconeogenesis about -16 kJ/mol (-3.83 kcal/mol), namely, both the pathways are irreversible.
The irreversibility of the glycolytic pathway is due to three strongly exergonic reactions, that cannot be used in gluconeogenesis, and listed below.

• The phosphorylation of glucose to glucose 6-phosphate, catalyzed by hexokinase (EC 2.7.1.1) or glucokinase (EC 2.7.1.2).
  ?G = -33.4 kJ/mol (-8 kcal/mol)
  ?G°’ = -16.7 kJ/mol (-4 kcal/mol)
• The phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate, catalyzed by phosphofructokinase-1 or PFK-1 (EC 2.7.1.11)
  ?G = -22.2 kJ/mol (-5.3 kcal/mol)
  ?G°’ = -14.2 kJ/mol (-3.4 kcal/mol)
• The conversion of phosphoenolpyruvate or PEP to pyruvate, catalyzed by pyruvate kinase (EC 2.7.1.40)
  ?G = -16.7 kJ/mol (-4.0 kcal/mol)
  ?G°’ = -31.4 kJ/mole (-7.5 kcal/mol)