title: Ontogeny of the murine glucose-6-phosphatase system.
abstract: A deficiency in microsomal glucose-6-phosphatase (G6Pase) activity causes glycogen storage disease type 1 (GSD-1), a clinically and biochemically heterogeneous group of diseases. It has been suggested that catalysis by G6Pase involves multiple components, with defects in the G6Pase catalytic unit causing GSD-1a and defects in the putative substrate and product translocases causing GSD-1b, 1c, and 1d. However, this model is open to debate. To elucidate the G6Pase system, we have examined G6Pase mRNA expression, G6Pase activity, and glucose 6-phosphate (G6P) transport activity in the murine liver and kidney during normal development. In the liver, G6Pase mRNA and enzymatic activity were detected at 18 days gestation and increased markedly at parturition, before leveling off to adult levels. In the kidney, G6Pase mRNA and enzymatic activity appeared at 19 days gestation and peaked at weaning, suggesting that kidney G6Pase may have a different metabolic role. In situ hybridization analysis demonstrated that, in addition to the liver and kidney, the intestine expressed G6Pase. Despite the expression of G6Pase in the embryonic liver, microsomal G6P transport activity was not detectable until birth, peaking at about age 4 weeks. Our study strongly supports the multicomponent model for the G6Pase system.
authors.affiliation: Heritable Disorders Branch, National Institute of Child Health and Human Development, Bethesda, Maryland, 20892, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Pan
authors.forename: K J
authors.initials: KJ
authors.lastname: Lei
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: J M
authors.initials: JM
authors.lastname: Ward
authors.forename: J Y
authors.initials: JY
authors.lastname: Chou
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport; D002384:Catalysis; D005314:Embryonic and Fetal Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005952:Glucose-6-Phosphatase / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D007422:Intestines / Q000201:enzymology / Q000254:growth & development; D007668:Kidney / Q000201:enzymology / Q000254:growth & development; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology; D009928:Organ Specificity / Q000235:genetics
chemical_list: D005952:Glucose-6-Phosphatase