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Science 22 October 1993:
Vol. 262. no. 5133, pp. 580 - 583
DOI: 10.1126/science.8211187
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Articles

Science, Vol 262, Issue 5133, 580-583
Copyright © 1993 by American Association for the Advancement of Science

articles

Mutations in the glucose-6-phosphatase gene that cause glycogen storage disease type 1a

KJ Lei, LL Shelly, CJ Pan, JB Sidbury, and JY Chou

Human Genetics Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.

Glycogen storage disease (GSD) type 1a is caused by the deficiency of D-glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. Despite both a high incidence and morbidity, the molecular mechanisms underlying this deficiency have eluded characterization. In the present study, the molecular and biochemical characterization of the human G6Pase complementary DNA, its gene, and the expressed protein, which is indistinguishable from human microsomal G6Pase, are reported. Several mutations in the G6Pase gene of affected individuals that completely inactivate the enzyme have been identified. These results establish the molecular basis of this disease and open the way for future gene therapy.


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D. Argaud, T. L. Kirby, C. B. Newgard, and A. J. Lange (1997)
J. Biol. Chem. 272, 12854-12861
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From phosphatases to vanadium peroxidases: A similar architecture of the active site.
W. Hemrika, R. Renirie, H. L. Dekker, P. Barnett, and R. Wever (1997)
PNAS 94, 2145-2149
   Abstract »    Full Text »    PDF »
Glucose Regulates in Vivo Glucose-6-phosphatase Gene Expression in the Liver of Diabetic Rats.
D. Massillon, N. Barzilai, W. Chen, M. Hu, and L. Rossetti (1996)
J. Biol. Chem. 271, 9871-9874
   Abstract »    Full Text »    PDF »
Glucose Transport and Glucose 6-Phosphate Hydrolysis in Intact Rat Liver Microsomes.
J.-F.ço. St-Denis, A. Berteloot, H. Vidal, B. Annabi, and Gér. van de Werve (1995)
J. Biol. Chem. 270, 21092-21097
   Abstract »    Full Text »    PDF »
Evidence for a Membrane Exchangeable Glucose Pool in the Functioning of Rat Liver Glucose-6-phosphatase.
A. Berteloot, J.-F.ço. St-Denis, and Gér. van de Werve (1995)
J. Biol. Chem. 270, 21098-21102
   Abstract »    Full Text »    PDF »
Structure-Function Analysis of Human Glucose-6-phosphatase, the Enzyme Deficient in Glycogen Storage Disease Type 1a.
K.-J. Lei, C.-J. Pan, J.-L. Liu, L. L. Shelly, and J. Y. Chou (1995)
J. Biol. Chem. 270, 11882-11886
   Abstract »    Full Text »    PDF »
Overexpression of the P46 (T1) Translocase Component of the Glucose-6-phosphatase Complex in Hepatocytes Impairs Glycogen Accumulation via Hydrolysis of Glucose 1-Phosphate.
J. An, Y. Li, G. van de Werve, and C. B. Newgard (2001)
J. Biol. Chem. 276, 10722-10729
   Abstract »    Full Text »    PDF »
Cellular Release of [18F]2-Fluoro-2-deoxyglucose as a Function of the Glucose-6-phosphatase Enzyme System.
C. Caraco, L. Aloj, L.-Y. Chen, J. Y. Chou, and W. C. Eckelman (2000)
J. Biol. Chem. 275, 18489-18494
   Abstract »    Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)