Membrane , glucose-6-phosphatase

Because the primary eveuts between insulin binding to its receptor and glucose transport are signal transduction events, a role for chromodulin in these events has been probed. Chromoduhn activates the tyrosine kinase activity of insulin-activated insulin receptor and activates a membrane phosphotyrosine phosphatase in adipocyte membranes. The addition of bovine liver chromodulin to rat adipocytic membranes in the presence of insuhn results in a concentration-dependent eightfold stimulation of insulin-dependent protein tyrosine kinase activity (while no activation... 

FIGURE 23.8 Glu cose-6-phosphatase is localized in the endoplasmic reticulum membrane. Conversion of glucose-6-phosphate to glucose occurs during transport into the ER. 

Sukalski, K. A., and Nordlie, R. C., 1989. Glucose-6-phosphatase Two concepts of membrane-funcdon relationship. Advances in Enzymology 62 93-117. 

Transporters in the plasma membrane of hepatocytes allow insulin-independent transport of glucose and other sugars in both directions. In contrast to muscle, the liver possesses the enzyme glucose-6-phosphatase, which can release glucose from glucose-6-phosphate. 

The amount of total enzymatic activity that becomes manifest only after disruption of membranous barriers between enzyme and substrate or upon removal of some otherwise inhibitory factor. Membrane disruption is often achieved by treatment with detergent to solubihze the enzyme. One example is the so-called microsomal glucose-6-phosphatase, an enzymatic activity that is located in the lumen of the endoplasmic reticulum but becomes trapped as a latent activity in microsome vesicles upon mechanical disruption of cells. 

The release of glucose from the glycogen stores in the liver is mediated by glucose 6-phosphatase, which is apparently embedded within the membranes of the endoplasmic reticulum. A labile enzyme, it consists of a 357-residue catalytic subrmit,251/252 which may be associated with other subunits that participate in transport.252 253 A deficiency of this enzyme causes the very severe type la glycogen storage disease (see Box 20-D).251 253 Only hepatocytes have significant glucose 6-phosphatase activity. 

Although the enzyme sediments with intact cells, alkaline phosphatase appears in the supernate when broken cells are centrifuged. Malamy and Horecker (5) discovered that alkaline phosphatase is quantitatively released from the cell when E. coli are converted to spheroplasts by lysozyme and ethylenediaminetetraacetic acid (EDTA) in a sucrose medium. This evidence, supported by the observation that substrates such as glucose 6-phosphate are rapidly hydrolyzed by intact cells with release of most of the phosphate into the medium, led Malamy and Horecker (6) to suggest that alkaline phosphatase is localized in the periplasmic space, a region described by Mitchell (7) as lying between the protoplasmic membrane and the wall layer, and that it is not in association with the wall (8). 

Although glucose-6-phosphatase activity in the nuclear fraction which has generally been observed may in part result from contamination of nuclear preparations with unruptured cells and debris, activity has also been observed with purified nuclei (62). Further, Kashnig and Kasper (63) have recently identified glucose-6-phosphatase as a component of rat liver nuclear membrane. 

D. Possible Significance of the Membranous Nature of Glucose-6-phosphatase... 

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