Glucose-6-phosphatase dependent substrate transport in the glycogen storage disease type-1a mouse.
Glycogen storage disease type 1a (GSD-1a) is caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. A G6Pase knockout mouse which mimics the pathophysiology of human GSD-1a patients was created to understand the pathogenesis of this disorder, to delineate the mechanisms of G6Pase catalysis, and to develop future therapeutic approaches. By examining G6Pase in the liver and kidney, the primary gluconeogenic tissues, we demonstrate that glucose-6-P transport and hydrolysis are performed by separate proteins which are tightly coupled. We propose a modified translocase catalytic unit model for G6Pase catalysis.
Lei
K J
KJ
Heritable Disorders Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Chen
H
H
Pan
C J
CJ
Ward
J M
JM
Mosinger
B
B
Lee
E J
EJ
Westphal
H
H
Mansfield
B C
BC
Chou
J Y
JY
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001692:Biological Transport; D001786:Blood Glucose / Q000032:analysis; D005952:Glucose-6-Phosphatase / Q000235:genetics* / Q000378:metabolism*; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000235:genetics / Q000378:metabolism; D005953:Glycogen Storage Disease Type I / Q000201:enzymology* / Q000209:etiology* / Q000235:genetics; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D008969:Molecular Sequence Data; D010641:Phenotype
D001786:Blood Glucose; D005958:Glucosephosphates; D019298:Glucose-6-Phosphate; D005952:Glucose-6-Phosphatase