Biochemical Journal

Review article

The glucose-6-phosphatase system

Emile van SCHAFTINGEN, Isabelle GERIN


Glucose-6-phosphatase (G6Pase), an enzyme found mainly in the liver and the kidneys, plays the important role of providing glucose during starvation. Unlike most phosphatases acting on water-soluble compounds, it is a membrane-bound enzyme, being associated with the endoplasmic reticulum. In 1975, W. Arion and co-workers proposed a model according to which G6Pase was thought to be a rather unspecific phosphatase, with its catalytic site oriented towards the lumen of the endoplasmic reticulum [Arion, Wallin, Lange and Ballas (1975) Mol. Cell. Biochem. 6, 75–83]. Substrate would be provided to this enzyme by a translocase that is specific for glucose 6-phosphate, thereby accounting for the specificity of the phosphatase for glucose 6-phosphate in intact microsomes. Distinct transporters would allow inorganic phosphate and glucose to leave the vesicles. At variance with this substrate-transport model, other models propose that conformational changes play an important role in the properties of G6Pase. The last 10 years have witnessed important progress in our knowledge of the glucose 6-phosphate hydrolysis system. The genes encoding G6Pase and the glucose 6-phosphate translocase have been cloned and shown to be mutated in glycogen storage disease type Ia and type Ib respectively. The gene encoding a G6Pase-related protein, expressed specifically in pancreatic islets, has also been cloned. Specific potent inhibitors of G6Pase and of the glucose 6-phosphate translocase have been synthesized or isolated from micro-organisms. These as well as other findings support the model initially proposed by Arion. Much progress has also been made with regard to the regulation of the expression of G6Pase by insulin, glucocorticoids, cAMP and glucose.

  • gluconeogenesis
  • glucose 6-phosphate
  • glycogen
  • glycogen storage disease
  • transporter


  • 2 Present address: Department of Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, U.S.A.

  • Abbreviations used: AICAriboside, 5-amino-4-imidazolecarboxamide riboside; AICAR, 5-amino-4-imidazolecarboxamide ribotide; DIDS, 4,4′-di-isothiocyanostilbene-2,2′-disulphonate; Glc-6-P, glucose 6-phosphate; G6Pase, glucose-6-phosphatase; GSD, glycogen storage disease; HNF, hepatocyte nuclear factor; Man-6-P, mannose 6-phosphate.