Glucogenesis 24

• Gluconeogenesis


  Synthesis of glucose or glycogen from non carbohydrates like pyruvate, lactate glucogenic amino acids, glycerol and propionic acid

  
• Gluconeogenesis


  • Mainly occurs in cytosol
  • Some precursors are produced in mitochondria
  • Takes place in liver and kidney
  • Involves steps of TCA cycle and reversal of glycolysis
  • The irreversible steps of glycolysis are catalysed by Hexokinase, Phosphofructokinase and Pyruvate kinase, which are bypassed by alternate enzymes specific to gluconeogenesis

  
• Key enzymes of gluconeogenesis

  • Pyruvate carboxylase
  • Phosphoenolpyruvate carboxykinase (PEPCK)
  • Fructose 1,6- Bis phosphatase
  • Glucose 6-phosphatase

  
• The pathway of gluconeogenesis meets the needs of the body for glucose, providing a continuous supply as a source of energy for the CNS, Brain, RBC and skeletal muscle during starvation

  
• Substrates for Gluconeogenesis


  • Gly, Ala, Ser, Thr, Cys, Trp -> pyruvate -> oxaloacetate
  • Phe, Tyr -> fumarate
  • Asp, Asn -> oxaloacetate
  • Arg, His,Glu, gln, pro -> KG -> oxaloacetate -> Glucose
  • Val, isoleucine, Met -> succinyl CoA
  • Propionyl CoA -> succinyl CoA -> oxaloacetate

  
• Cori's Cycle


  Glucose/Glycogen converted to lactate in the muscle and this lactate is converted back to glucose in liver

  
• During active muscle contraction glycogen breaks down to generate glucose

  
• Regulation of gluconeogenesis


  • Glucagon and the availability of substrates mainly regulate gluconeogenesis
  • Glucagon & glucocorticoid stimulate gluconeogenesis
  • Insulin inhibit gluconeogenesis
  • Glucogenic amino acids have stimulating effect on key gluconeogenic enzymes
  • Acetyl CoA promotes gluconeogenesis
  • Starvation causes excessive lipolysis in adipose tissues, leading to accumulation of acetyl CoA in the liver, which stimulates gluconeogenic enzymes