Gluconeogenesis

• 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 of glucose 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, but the muscle lacks the enzyme Glu-6P to convert the glucose back to glycogen, so the liver performs this conversion

  
• Regulation of gluconeogenesis

  • Glucagon and glucocorticoid stimulate gluconeogenesis
  • Insulin inhibits 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

  
• Deficiency of b12 enzyme can affect gluconeogenesis
• What is the rate limiting enzyme for Gluconeogenesis?

  Fructose-1,6-bisphosphatase
• What inhibits the rate limiting enzyme in Gluconeogenesis?

  Fructose-2,6-bisphosphate and AMP
• When does Gluconeogenesis occur?

  During fasting, low carbohydrate intake, or intense exercise.
• What inhibits Glucose 1-6 phosphatase?

  Insulin
• What inhibits Fructose 1-6 bisphosphatase?

  AMP and F-2-6 Bisphosphate
• What is the process of Gluconeogenesis?

  Reverse glycolysis
• How does adrenaline contribute to Gluconeogenesis?

  Stimulation of PECK enzyme
• How does Glucagon contribute to Gluconeogenesis?

  Stimulates Gluconeogenesis enzymes