Development, glucose-6-phosphatase

The enzyme pattern of the placenta varies with the stage of development. For example, although early in development the placenta (in contrast to the fetal liver) has high glucose-6-phosphatase activity and glycogen content, placental glycogen and glucose-phosphatase activities are low at term. 

A 73 year old Japanese woman, weight 33.5 kg, took nateglinide 270 mg/day and pioglitazone 15 mg/day for 6 months (105). Her HbAic concentration was 8.6% and fasting glucose 11.4 mmol/1. Metformin 250 mg bd was added and 3 weeks later she developed jaundice and fatigue. A few months before her liver function tests had been normal. Aspartate transaminase activity was 689 IU/1, alanine transaminase 772 IU/1, alkaline phosphatase 639 IU/1, and bilirubin 6.5 mg/dl. All oral therapy was withdrawn and insulin started. Her liver function improved over the next few weeks. 

We have developed two methods for the synthesis of natural and unnatural products from D-glucose. Enantio-and diastereo-switching method established a new strategy for the synthesis of four possible stereomers for natural products synthesis, and this powerful method was successfully applied to the synthesis of unnatural protein phosphatase inhibitors. The second synthetic method involved the preparation of the urea-glycosidic linkages for the synthesis of glycopeptide mimics. 

Luminescent endpoints are available for all of the commonly used enzyme labels, including horseradish peroxidase, alkaline phosphatase, glucose-6-phosphate dehydrogenase, glucose oxidase, and P-galactosidase. Detection limits in the subattomolar range have been attained (34). Chemiluminescent assays for novel enzyme labels such as xanthine oxidase have also been developed (50). 

Vanadate (VOj or H2VO4 ) was first recognized in 1979 as having insulin mimetic properties [258]. Since then, vanadate and vanadyl (V ) have been shown to mimic most but not all biological actions of insulin in vitro and to lower blood glucose in streptozotocin-treated rats [259, 260]. Vanadate is a potent inhibitor of phosphotyrosine phosphatases, an interesting activity since the insulin receptor is a tyrosine kinase, and some of the actions of insulin have been proposed to take place via autophosphorylation of the insulin receptor and phosphorylation of cellular substrates on tyrosine residues [261]. Some recent developments on the mechanism and the in vivo activity of vanadate and its derivatives are presented here. 

Individuals with a glucose-6-phosphatase (G-6-P —> Glucose, in the liver) deficiency develop a glycogen storage disease. This condition results in hypoglycemia, low blood sugar, accumulation of lactic acid and ketones. Distal kidney tubule excretion of uric acid is inhibited and hyperuricemia (XS uric acid) and gout results. 

The direct detection of electrochemical labels entails problems with sensitivity. For this reason the majority of electrochemical immimoassay development has focused on the measurement of enzyme labels by detection of eiectroactive products arising from enzyme catalyzed reactions. A wide variety of enzyme labels have been used for electrochemical immunoassays. These include glucose oxidase, glucose-6-phosphate dehydrogenase and alkaline phosphatase. ... 

Naphthalene ingestion can result in acute as well as delayed toxicity. The primary target organs of toxicity are the blood and eyes. Individuals deficient in glucose-6-phosphatase dehydrogenase are especially sensitive to the hemolytic effects of naphthalene. Normal individuals may also develop hemolysis when exposed to high doses. 

We have developed preparative enzymatic syntheses of several unusual hexoketoses using fructose-1,6-diphosphate aldolase (FDP-aldolase, E.C.4.1.2.13) as catalyst and dihydroxyacetone phosphate (DHAP) and an aldehyde as substrates (15). The enzyme appears to be very specific for DHAP but will accept a variety of aldehydes as acceptors. The ketose-1-phosphates prepared are converted to the phosphate free ketoses after removal of the phosphate group by acid- or phosphatase-catalyzed hydrolysis. The ketoses can be isomerized stereospecifically to aldoses catalyzed by glucose isomerase (E.C.5.3.1.5.) from Flavobacteriuum arborescens. The equilibrium mixtures of aldoses and ketoses are then separated by chromatography on Dowex 50 (Ba ) or Dowex 1 (HSO "). Figure 1 illustrates the preparation of a mixture of 6-deoxy-6-fluoro-D-fructose... 

Asotra, K. (1986). Glucose-6-phosphatase activity in rtormal and denervated developing chick gastrocnemii reappraisal of glycogenolytic and glycolytic metabolism in skeletal muscle. Exp. Path., 29, 103-12. 

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