Disorders of Gluconeogenesis

  • N. R. M. Buist


Gluconeogenesis is defined as the net formation of glucose from non-carbohydrate precursors such as pyruvate, lactate, glycerol, and certain amino acids. It is crucial for survival because glucose, the primary substrate for a number of tissues, most notably the brain, is only available during feeding, and liver glycogen stores can only provide glucose for a few hours. Gluconeogenesis and glycolysis have many enzymes in common (Fig. 1). Exceptions are the enzymes that catalyze the four irreversible steps which ensure a unidirectional flux from pyruvate to glucose:
  • Pyruvate carboxylase (PC)

  • Phosphoenolpyruvate carboxykinase (PEPCK)

  • Fructose-1,6-bisphosphatase (FBPase)

  • Glucose-6-phosphatase (G-6-Pase)

Defects of all four gluconeogenic enzymes are known Common to all are the tendency to facile hypoglycemia induced by fasting and lactic acidosis due to failure to recycle lactate to glucose. The deficiency of G-6Pase (Chap. 5) and FBPase usually spare the brain, unless it is damaged by recurrent hypoglycemia. The deficiencies of PEPCK and PC are associated with a progressive neurodegenerative disorder which is usually fatal.


Lactic Acidosis Pyruvate Carboxyla Renal Tubular Acidosis Metabolic Derangement Culture Skin Fibroblast 
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© Springer-Verlag Berlin Heidelberg 1995

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  • N. R. M. Buist

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