GluconeogenesisFormation of glucose from non-carbohydrate source
• occurs mainly in liver and• to a limited extent in kidney & small intestine• Synthesis of glucose from pyruvate utilizes many of the same enzymes as Glycolysis• Three Glycolysis reactions have such a large negative ∆G that they are essentially irreversible Hexokinase (or Glucokinase) Phosphofructokinase Pyruvate KinaseThese steps must be bypassed in Gluconeogenesis.The first two of the bypass reactions involve simple hydrolysis reactions
Glucose-6-phosphatase 6 CH OPO 2− CH2OH 2 3 5 O O H H H H H H2O H 4 OH H 1 OH H + Pi OH OH OH OH 3 2 H OH H OH glucose-6-phosphate glucoseGlucose-6-Phosphatase (Gluconeogenesis) catalyzes: glucose-6-phosphate + H2O glucose + PiThis enzyme is embedded in the endoplasmicreticulum (ER) membrane in liver cells
Phosphofructokinase → 6 CH OPO 2− 1CH2OH 6 CH OPO 2− 1CH2OPO32− 2 3 2 3 O ATP ADP O 5 H HO 2 5 H HO 2 H 4 3 OH H 4 3 OH Pi H2O OH H OH H fructose-6-phosphate fructose-1,6-bisphosphate ← Fructose-1,6-bisphosphatase Fructose-1,6-biosphosphataseFructose-1,6-bisphosphatase (Gluconeogenesis) catalyzes: fructose-1,6-bisP + H2O fructose-6-P + Pi
Bypass of Pyruvate Kinase:Pyruvate Kinase (last step of Glycolysis) catalyzes: phosphoenolpyruvate + ADP pyruvate + ATPFor bypass of the Pyruvate Kinase reaction, 2 ~P bonds isrequired.
Pyruvate Carboxylase PEP Carboxykinase O O− O− C O− O O C ATP ADP + Pi C O GTP GDP C C O CH2 C OPO32− HCO3− C CO2 CH3 CH2 O O− pyruvate oxaloacetate PEPBypass of Pyruvate Kinase (2 enzymes):Pyruvate Carboxylase (Gluconeogenesis) catalyzes: pyruvate + HCO3− + ATP oxaloacetate + ADP + PiPEP Carboxykinase (Gluconeogenesis) catalyzes: oxaloacetate + GTP PEP + GDP + CO2