Gluconeogenesis, irreversible enzymes
- Pathway Produces Fresh Glucose.
||In mitochondria. Pyruvate → oxaloacetate.
||Requires biotin, ATP. Activated by acetyl-CoA.
||In cytosol. Oxaloacetate → phosphoenolpyruvate.
||In cytosol. Fructose-1,6-bisphosphate → fructose-6-phosphate.
||Citrate ⊕, AMP ⊝, fructose 2,6-bisphosphate ⊝.
||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.