Glucose-1 -phosphatase

Extracts of rat liver, free of phosphoglucomutase and phosphofructo-isomerase, contain an enzyme which specifically hydrolyzes glucose-6-phosphate to free glucose. Other substrates are inert. The enzyme is 

As mentioned in the Introduction, G-6-Pase was one of the first enzymes shown to be inactivated by treatment with phospholipases (Beaufay and DeDuve, 1954). Studies in this laboratory have demonstrated, however, that treatment of microsomes with phospholipase A does not directly inactivate G-6-Pase (Zakim, 1970). Instead, treatment of microsomes for short periods of time with small amounts of purified phospholipase A from Naja naja venom produces an unstable form of G-6-Pase. The phospholipase-A-treated form of G-6-Pase can be stabilized by albumin and phospholipid micelles. In fact, with proper selection of the conditions for treatment of microsomes with phospholipase A, and subsequently with albumin, the activity of G-6-Pase can be increased to levels greater than those in untreated microsomes. The exact role of albumin in activating G-6-Pase that has been treated with phospholipase A is not understood completely, but it is not related to binding of fatty acids released by the actions of phospholipase A. 

Since G-6-Pase is not inactivated directly by treatment with phospholipase A, these experiments indicate that this enzyme does not have an absolute dependence for activity on the phospholipid configuration present in the native microsome. More importantly, the activity of G-6-Pase in untreated microsomes is less than its maximum potential activity at 17niax  

Studies of the action of phospholipase C on the activity of G-6-Pase yield further insights into the mechanism of the effects of phospholipase A on activity. The effects of phospholipase C (Clostridium welchii) on G-6-Pase differ from those of phospholipase A in that the action of 

In addition to altering the maximum potential activity of glucose-6-phosphatase, treatment with phospholipase A leads to a reversible increase in the affinity of this enzyme for glucose-6-phosphate (G-6-P), and to differential stabilities in the PPj-glucose phosphotransferase activity and in the PPi- and glucose-6-P-phosphohydrolase activities of the enzyme. All of these activities (equations la, lb, 2, and 3, below) have been shown to be common to one enzyme (cf., Nordlie and Arion, 1964). 

After treatment with phospholipase A, the phosphotransferase activity of G-6-Pase is unstable at pH 5.75 but stable at pH 8, whereas the phos-phohydrolase activity is unstable at pH 8.0 but may be stabilized at pH 5.75 by G-6-P or PP. As a result, with proper selection of experimental conditions, preparations with variable phosphotransferase and phos-phohydrolase activities can be made (Zakim, 1970). As alluded to above, treatment with phospholipase C also has differential actions on these phosphotransferase and phosphohydrolase activities of the enzyme. 

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

Recently, two examples of the separation of enantiomers using CCC have been published (Fig. 1-2). The complete enantiomeric separation of commercial d,l-kynurenine (2) with bovine serum albumin (BSA) as a chiral selector in an aqueous-aqueous polymer phase system was achieved within 3.5 h [128]. Moreover, the chiral resolution of 100 mg of an estrogen receptor partial agonist (7-DMO, 3) was performed using a sulfated (3-cyclodextrin [129, 130], while previous attempts with unsubstituted cyclodextrin were not successful [124]. The same authors described the partial resolution of a glucose-6-phosphatase inhibitor (4) with a Whelk-0 derivative as chiral selector (5) [129]. 

Gluconeogenesis 1 TORC2, others l Expression PEP carboxykinase, glucose-6-phosphatase Liver... 

Metformin restrains hepatic glucose production principally by suppression of gluconeogenesis. The mechanisms involve potentiation of insulin action and decreased hepatic extraction of certain gluconeogenic substrates such as lactate. In addition, metformin reduces the rate of hepatic glycogenolysis and decreases the activity of hepatic glucose-6-phosphatase. Insulin-stimulated glucose uptake and glycogenesis by skeletal muscle is increased by metformin mainly by increased... 

Type 1 Von Gierke s disease Deficiency of glucose-6-phosphatase Liver cells and renal tubule cells loaded with glycogen. Hypoglycemia, lactic-acidemia, ketosis, hyperlipemia. 

Glucose-6-phosphatase T T Glucocorticoids, glucagon, epinephrine (cAMP) Insulin ... 

Purine overproduction and hyperuricemia in von Gierke s disease (glucose-6-phosphatase deficiency)... 

Skeletal muscle cannot contribute directly to blood glucose because it does not contain glucose-6-phosphatase. 

The free glucose produced by this reaction is supplied to the blood from the tissues. As exemplified by gluconeogenesis, one may easily envision the economical organization of these metabolic routes, since, apart from four special gluconeogenesis enzymes-pyruvate carboxylase, phosphopyruvate carboxylase, fructose bisphosphatase, and glucose 6-phosphatase-individual glycolytic enzymes are also used in the gluconeogenesis. 

Another class of carbohydrate and fatty acid metabolism disorders is caused by systemic metabolic defects that affect the brain. Glucose-6-phosphatase deficiency (glycogenosis type I, Von Gierke s disease)... 

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