On the involvement of a glucose 6-phosphate transport system in the function of microsomal glucose 6-phosphatase

Abstract

A model for microsomal glucose 6-phosphatase (EC 3.1.3.9) is presented. Glucose 6-phosphatase is postulated to be resultant of the coupling of two components of the microsomal membrane: 1) a glucose 6-phosphate - specific transport system which functions to shuttle the sugar phosphate from the cytoplasm to the lumen of the endoplasmic reticulum; and 2) a catalytic component, glucose-6-P phosphohydrolase, bound to the luminal surface of the membrane. A large body of existing data was shown to be consistent with this hypothesis. In particular, the model reconciles well-documented differences in the kinetic properties of the enzyme of untreated and modified microsomal preparations. Characteristic responses of the enzyme to changes in nutritional and hormonal states may be attributed to adaptations which alter the relative capacities of the transport and catalytic components.

Demonstration of a Metabolically Active Glucose-6-phosphate Pool in the Lumen of Liver Microsomal Vesicles

“…A transmembrane gradient of glucose-6-phosphate is present at all extravesicular glucose-6-phosphate concentrations studied, which is consistent with the phenomenon of latency exhibited by glucose-6-phosphatase activity; the lower intravesicular concentration of glucose-6-phosphate can account for the higher K m value of glucose-6-phosphatase in native microsomal vesicles (15). The reduction of vesicular glucose-6-phosphate space at higher extravesicular glucose-6-phosphate concentration means that the hydrolytic capacity is higher than that of the transport, in accord with the rate-limiting property of the latter.…”

“…Presently there are essentially two models to explain it. According to the "translocase-catalytic unit" or "substrate transport" model (15)(16)(17)(18), the catalytic site of the glucose-6-phosphatase enzyme, situated inside the lumen of the ER (16), acts in concert with at least three putative ER transport proteins for the substrate glucose-6-phosphate and for the products phosphate and glucose, which have been named T1, T2, and T3 (2,12,16,18), respectively. In the "combined conformational flexibility-substrate transport model" (19 -21), there is no T1 transport protein.…”

“…after removal of the microsomal membrane barrier (15,16). It was subsequently observed that various GSD 1 patients lack the enzyme activity in native but not in disrupted microsomes (2) and, most importantly, that the enzyme activities of these patients behave as predicted by the original substrate transport model (22)(23)(24).…”

Cloning and sequencing of the 5′ region of the human glucose‐6‐phosphatase gene: transcriptional regulation by cAMP, insulin and glucocorticoids in H4IIE hepatoma cells

“…There have been some reports in the literature ind cating that glucocorticoids (dexamethasone) increase liver g ucose-6-phosphatase enzyme activity and others showing tlat it does not (e.g. [1,12,14,[22][23][24][25][26][27]). A simple explanation fi,r these apparently conflicting findings would be that the effect of dexamethasone also depends on the levels of other h )rmones like insulin and glucagon as illustrated in Table 1.…”

Glycogen storage disease type Ib: A defect in the glucose-6-phosphate transport system in microsomal membrane

“…Therefore, the patient was diagnosed as GSD Type Ib. Arion et al (1975) postulated that G6Pase activity results from the coupling of two components of the microsomal membrane: 1) a glucose-6-phosphate-specific transport system which functions to shuttle G6P from the cytoplasm to the lumen of endoplasmic reticulum; and 2) a catalytic component, glucose-6-phosphate phosphohydrolase, bound to the luminal surface of the membrane.…”