Mammalian carbamyl phosphate: Glucose phosphotransferase and glucose-6-phosphate phosphohydrolase: Extended tissue distribution

Colilla, William; Jorgenson, Roger A.; Nordlie, Robert C.

doi:10.1016/0005-2744(75)90292-2

Cited by 45 publications

(14 citation statements)

References 28 publications

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“…More recently, the presence of the multifunctional enzyme has been demonstrated in pancreatic islet cells (101), with a specific activity in microsomes derived therefrom exceeding that in liver (104). All of these organs and tissues, in their own unique fashions, contribute to and impact upon blood glucose in health and disease.…”

Section: A Proposed Integrated Coordinated Mechanism Involving Hydromentioning

confidence: 98%

Glucose-6-Phosphatase Structure, Regulation, and Function: An Update

Foster¹,

Pederson²,

Nordlie³

1997

Experimental Biology and Medicine

106

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Work on the glucose-6-phosphatase system has intensified and diversified extensively in the past 3 years. The gene for the catalytic unit of the liver enzyme has been cloned from three species, and regulation at the level of gene expression is being studied in several laboratories worldwide. More than 20 sites of mutation in the catalytic unit protein have been demonstrated to underlie glycogenesis type 1a. inhibition of glucose-6-P hydrolysis by several newly identified competitive and time-dependent, irreversible inhibitors has been demonstrated and in several instances the predicted effects on liver glycogen formation and/or breakdown and on blood glucose production have been shown. Refinements in and additions to the presently dominant "substrate transport-catalytic unit" topological model for the glucose-6-phosphatase system have been made. A new model alternative to this, based on the "combined conformational flexibility-substrate transport" concept, has emerged. Experimental evidence for the phosphorylation of glucose in liver by high-K(m),glucose enzyme(s) in addition to glucokinase has continued to emerge, and new in vitro evidence supportive of biosynthetic functions of the glucose-6-phosphatase system in this role has appeared. High levels of multifunctional glucose-6-phosphatase have been shown present in pancreatic islet beta cells. Glucose-6-P has been established as the likely insulin secretagog in beta cells. Interesting differences in the temporal responses of glucose-6-phosphatase in kidney and liver have been demonstrated. An initial attempt is made here to meld the hepatic and pancreatic islet beta-cell glucose-6-phosphatase systems, and to a lesser extent the kidney tubular and small intestinal mucosal glucose-6-phosphatase systems into an integrated, coordinated mechanism involved in whole-body glucose homeostasis in health and disease.

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Section: A Proposed Integrated Coordinated Mechanism Involving Hydromentioning

confidence: 98%

Glucose-6-Phosphatase Structure, Regulation, and Function: An Update

Foster¹,

Pederson²,

Nordlie³

1997

Experimental Biology and Medicine

106

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“…The possibility that G6Pase may be per forming an alternative function may need to be consid ered. Postulated alternative functions for G6Pase in other sites include phosphohydrolysis of alternative substrates and phosphotransferase reactions [41]; glucose sensing (in islet cells), and intracellular calcium homeostasis [69]. The significance of these potential roles remains to be established even in extra-cranial tissues; the possibil ity of similar alternative functions in brain needs evalua tion.…”

Section: Discussionmentioning

confidence: 99%

“…Acid-and alkaline phosphatase are present in almost all tissues and remain a problem for histochemical detection of G6Pase enzyme activity [37]. The success of the autoradiographic and positronemission tomographic variants of the 2-deoxyglucose method for estimation of local cerebral metabolic rates, which assume minimal G6Pase activity, has added to the general conviction that brain does not contain specific G6Pase activity [38,39] despite several reports of low levels of such activity in brain [40,41 ]. However, double immunofluorescence studies on human brain tissue have shown G6Pase (co-localising with glial fibrillary acidic protein, GFAP) in some but not all astrocytes [42], Many mature process-bearing astrocytes in fetal and adult brain were positive for G6Pase, particularly those processes ending on blood vessels.…”

Section: Brain Glucose-6-phosphatasementioning

confidence: 99%

A Role for Astrocytes in Glucose Delivery to Neurons?

et al. 1996

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The present paper examines the possible role of astrocytes in the delivery of glycogen-derived glucose for neuronal metabolism. Such a process would require astrocytic expression of glucose-6-phosphatase. The degree and significance of brain expression of glucose-6-phosphatase (EC 3.1.3.9) has been a subject of controversy. Published immunohistochemical data are consistent with expression of glucose-6-phosphatase by astrocytes, both in vivo and in vitro. In this paper additional confirmation of the expression of glucose-6-phosphatase mRNA in rat brain is presented. Although cultured astrocytes demonstrate glucose-6-phosphatase activity in vitro under assay conditions, there is very limited in vitro evidence that this activity confers a glucose-export capacity on astrocytes. Under most conditions in vitro, lactate export predominates, however this may relate to aspects of the in vitro phenotype. Data relating to astrocytic glucose and lactate export are considered in the context of hypotheses of trafficking by astrocytes of substrates for neuronal metabolism, hypotheses that imply and require compartmentation of these substances, in contrast with current formulations of glucose transport into and within brain that imply no glucose compartmentation. Microdialysis studies of the properties of the brain extracellular fluid (ECF) glucose pool in the freely moving rat were performed seeking evidence of glucose compartmentation. Results of these studies do imply compartmentalisation of brain glucose, and are consistent with a model envisaging the majority of glucose reaching the neuron via the astrocytic intracellular space and the ECF. In addition, such studies provide evidence that rises in ECF glucose concentration are not the direct result of local recruitment of cerebral blood flow, but suggest the influence of intermediate, astrocyte-based mechanisms. Astrocytic glucose-6-phosphatase may permit astrocytes to modulate the transastrocytic flux of glucose to adjacent neurons in response to signals reflecting increased neuronal demand.

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“…Genetic defects affecting this enzyme cause glycogen storage disease type I which is a severe disease that leads to hypoglycaemia, acidosis, hepatomegaly and death if not recognized and treated properly. Glucose-6-phosphatase is primarily a liver enzyme but is also found in kidney, intestine and has been reported in other organs (Colilla et aL, 1975). Studying this enzyme in man is difficult because its activity is not present in white blood cells or cultured skin fibroblasts.…”

mentioning

confidence: 98%