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Query: EC:3.1.3.9 (
glucose-6-phosphatase
)
3,081
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The operation of glucose 6-phosphatase (
EC 3.1.3.9
) (Glc6Pase) stems from the interaction of at least two highly hydrophobic proteins embedded in the ER membrane, a heavily glycosylated catalytic subunit of m 36 kDa (
P36
) and a 46-kDa putative glucose 6-phosphate (Glc6P) translocase (P46). Topology studies of
P36
and P46 predict, respectively, nine and ten transmembrane domains with the N-terminal end of
P36
oriented towards the lumen of the ER and both termini of P46 oriented towards the cytoplasm.
P36
gene expression is increased by glucose, fructose 2,6-bisphosphate (Fru-2,6-P2) and free fatty acids, as well as by glucocorticoids and cyclic AMP; the latter are counteracted by insulin. P46 gene expression is affected by glucose, insulin and cyclic AMP in a manner similar to
P36
. Accordingly, several response elements for glucocorticoids, cyclic AMP and insulin regulated by hepatocyte nuclear factors were found in the Glc6Pase promoter. Mutations in
P36
and P46 lead to glycogen storage disease (GSD) type-1a and type-1 non a (formerly 1b and 1c), respectively. Adenovirus-mediated overexpression of
P36
in hepatocytes and in vivo impairs glycogen metabolism and glycolysis and increases glucose production;
P36
overexpression in INS-1 cells results in decreased glycolysis and glucose-induced insulin secretion. The nature of the interaction between
P36
and P46 in controling Glc6Pase activity remains to be defined. The latter might also have functions other than Glc6P transport that are related to Glc6P metabolism.
...
PMID:New lessons in the regulation of glucose metabolism taught by the glucose 6-phosphatase system. 1071 83
The final step of gluconeogenesis and glycogenolysis is catalyzed by the
glucose-6-phosphatase
(Glc-6-Pase) enzyme complex, located in the endoplasmic reticulum. The complex consists of a 36-kDa catalytic subunit (
P36
), a 46-kDa glucose 6-phosphate translocase (P46), and putative glucose and inorganic phosphate transporters. Mutations in the genes encoding
P36
or P46 have been linked to glycogen storage diseases type Ia and type Ib, respectively. However, the relative roles of these two proteins in control of the rate of glucose 6-phosphate hydrolysis have not been defined. To gain insight into this area, we have constructed a recombinant adenovirus containing the cDNA encoding human P46 (AdCMV-P46) and treated rat hepatocytes with this virus, or a virus encoding
P36
(AdCMV-
P36
), or the combination of both viruses, resulting in large and equivalent increases in expression of the transgenes within 8-24 h of viral treatment. The overexpressed P46 protein was appropriately targeted to hepatocyte microsomes and caused a 58% increase in glucose 6-phosphate hydrolysis in nondetergent-treated (intact) microsomal preparations relative to controls, whereas overexpression of
P36
caused a 3.6-fold increase. Overexpression of P46 caused a 50% inhibition of glycogen accumulation in hepatocytes from fasted rats incubated at 25 mm glucose relative to cells treated with a control virus (AdCMV-betaGAL). Furthermore, in hepatocytes from fed rats cultured at 25 mm glucose and then exposed to 15 mm glucose, AdCMV-P46 treatment activated glycogenolysis, as indicated by a 50% reduction in glycogen content relative to AdCMV-betaGAL-treated controls. In contrast, overexpression of P46 had only small effects on glycolysis, whereas overexpression of
P36
had large effects on both glycogen metabolism and glycolysis, even in the presence of co-overexpressed glucokinase. Finally, P46 overexpression enhanced glucose 1-phosphate but not fructose 6-phosphate hydrolysis in intact microsomes, providing a mechanism by which P46 overexpression may exert its preferential effects on glycogen metabolism.
...
PMID:Overexpression of the P46 (T1) translocase component of the glucose-6-phosphatase complex in hepatocytes impairs glycogen accumulation via hydrolysis of glucose 1-phosphate. 1114 7
