Gluconeogenesis, irreversible enzymes

  • Pathway Produces Fresh Glucose.
Pyruvate carboxylase In mitochondria. Pyruvate → oxaloacetate. Requires biotin, ATP. Activated by acetyl-CoA.
Phosphoenolpyruvate carboxykinase In cytosol. Oxaloacetate → phosphoenolpyruvate. Requires GTP.
Fructose-1,6-bisphosphatase In cytosol. Fructose-1,6-bisphosphate → fructose-6-phosphate. Citrate ⊕, AMP ⊝, fructose 2,6-bisphosphate ⊝.
Glucose-6-phosphatase In ER. Glucose-6-phosphate → glucose.  
  • Occurs primarily in liver; serves to maintain euglycemia during fasting. Enzymes also found in kidney, intestinal epithelium. Deficiency of the key gluconeogenic enzymes causes hypoglycemia. (Muscle cannot participate in gluconeogenesis because it lacks glucose-6-phosphatase).
  • Odd-chain fatty acids yield 1 propionyl-CoA during metabolism, which can enter the TCA cycle (as succinyl-CoA), undergo gluconeogenesis, and serve as a glucose source.
  • Even-chain fatty acids cannot produce new glucose, since they yield only acetyl-CoA equivalents.

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