Monday 26 September 2011

LSM2101 Part I Lecture 7 Gluconeogenesis


  • Synthesis of glucose from:
    • lactate
    • glycerol
    • glucogenic amino acids, e.g. alanine
    • odd fatty acid chains -> propionyl-CoA
  • Reverse of Glycolysis, but:
    • Hexokinase -> Glucose-6-phosphatase
    • Pyruvate Carboxylase: pyruvate -> oxaloacetate
    • PEPCK: oxaloacetate -> PEP
    • other enzymes are the same
  • Location: 90% liver, 10% kidney
    • Pyr Carboxylase: in mitochondria
    • PEPCK: in mitochondria or cytosol
    • Transfer from mitochondria -> cytosol:
      • Malate Route (generate NADH)
      • Aspartate Route
      • PEP channel
  • Regulations
    • Pyruvate Carboxylase: (+) acetyl-CoA
    • PFK: (+) AMP, F2,6BP (-)citrate,ATP vs. FBPase: (-) AMP, F2,6BP
    • PFK2: (+)AMP, Pi, F6P (-)citrate, ATP vs. FBPase2: (-) F6P (+)G3P 
  • Diseases
    • Deficient in Pyruvate Carboxylase: lactic acidosis, hypoglycemia
    • Deficient in FBP: no gluconeogenesis
  • Anaerobic glycolysis = production of lactate
    • in erythrocytes, tissues of eyes, skeletal muscle (short of ATP)
    • Recycle of lactate: Cori cycle, in liver
  • Adipose Tissue
    • store fatty acids as triacylglyceride
    • broken to: glycerol + FAs, transported to liver
    • Glycerol -> Glucose
    • FA (odd) -> propionyl-CoA -> succinyl-CoA -> glucose
  • Glucose-Alanine Cycle
    • Pyruvate -> Alanine (transamination), in muscles
    • Alanine -> Pyruvate, in liver