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Glucose-6-phosphatase structure, regulation, and function: an update

J D Foster1, B A Pederson, R C Nordlie

  • 1Department of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences, Grand Forks 58202, USA.

Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)
|September 1, 1997
PubMed
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Recent research advances the understanding of the glucose-6-phosphatase system, crucial for glucose homeostasis. New insights into gene regulation, mutations, inhibitors, and models are improving our grasp of its role in liver, pancreas, kidney, and intestine.

Area of Science:

  • Biochemistry and Molecular Biology
  • Endocrinology
  • Metabolic Regulation

Background:

  • The glucose-6-phosphatase (G6Pase) system is central to glucose homeostasis, primarily in the liver.
  • Recent years have seen significant advancements in understanding its molecular mechanisms and regulation.

Purpose of the Study:

  • To review and synthesize recent findings on the G6Pase system, including genetic, biochemical, and physiological aspects.
  • To explore the G6Pase system's role in various tissues and its integration into a whole-body glucose homeostasis model.

Main Methods:

  • Gene cloning and expression studies of the G6Pase catalytic unit.
  • Biochemical assays to characterize enzyme kinetics and inhibitor effects.
  • Analysis of mutations underlying Glycogenesis type 1a.

Related Experiment Videos

  • Development and refinement of topological and conceptual models of the G6Pase system.
  • Investigation of glucose phosphorylation and G6Pase activity in pancreatic islet beta cells, liver, kidney, and intestine.

    • Main Results:

    • The gene for the G6Pase catalytic unit has been cloned, with ongoing studies on gene expression regulation.
    • Over 20 mutations in the catalytic unit are linked to Glycogenesis type 1a.
    • New competitive and irreversible inhibitors of glucose-6-phosphate hydrolysis have been identified, with demonstrated effects on glucose metabolism.
    • Refined and alternative models, including the "substrate transport-catalytic unit" and "combined conformational flexibility-substrate transport" concepts, have been proposed.
    • Evidence supports high-Km glucose phosphorylation in liver and potential biosynthetic roles of the G6Pase system.
    • High levels of G6Pase are found in pancreatic islet beta cells, with glucose-6-phosphate identified as a likely insulin secretagog.
    • Distinct temporal responses of G6Pase in kidney and liver have been observed.

    Conclusions:

    • The G6Pase system is a complex, multifunctional entity with critical roles beyond hepatic glucose output.
    • Recent research has significantly advanced the understanding of G6Pase at the molecular and physiological levels.
    • An integrated model of G6Pase function across hepatic, pancreatic, renal, and intestinal systems is emerging, crucial for understanding whole-body glucose homeostasis in health and disease.