Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The intraperitoneal (IP) treatment of rats with diazinon (40 mg/kg) resulted in a variety of changes in the brain. Glycogen was depleted, but there was an increase in the activities of glycogen phosphorylase, phosphoglucomutase, hexokinase, lactate dehydrogenase, and fructose 1,6 diphosphatase. The activity of glucose-6-phosphatase was unaffected while that of cholinesterase was significantly reduced. Lactic acid content was increased, while that of pyruvate was not altered. Animals developed tremors and convulsions, which were maximal two hours after treatment. The induced changes may be compensatory mechanisms to provide extra energy to cerebral tissue as a result of the stimulatory effects in diazinon-treated animals.
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PMID:Cerebral glucose and glycogen metabolism in diazinon-treated animals. 350 78

Effect of diazinon (10,20 and 40 mg/kg, i.p.) on the level of blood glucose in rats was investigated. Hyperglycaemia peaked 2 h after i.p. treatment with 40 mg/kg diazinon. The cerebral acetylcholinesterase activity was significantly reduced. The blood level of pyruvic acid was unchanged while that of lactic acid was significantly increased. Convulsions and biochemical changes caused by diazinon (40 mg/kg) were prevented by diazepam injected immediately after diazinon. In diazinon-treated hyperglycaemic animals, the glycogen content of the brain was depleted, the activities of glycogen phosphorylase, phosphoglucomutase and hexokinase were significantly increased and the activity of glucose-6-phosphatase remained unchanged. Lactate dehydrogenase activity was also increased by treatment with diazinon. The induced changes may compensate for the energy requirement of stimulatory effects caused by diazinon.
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PMID:Changes in cerebral glycogenolysis and related enzymes in diazinon treated hyperglycaemic animals. 362 68

We studied 20 children with a clinical picture and laboratory study suggestive of hepatic glycogenosis. The age of the beginning of symptoms varied from birth to 24 months and the age at the diagnosis varied from 2 to 81 months. Hepatomegaly was found in all patients, diarrhea in 65% (13/26), "doll-face" in 55% (11/20) and convulsions in 50% (10/20). Nutritional evaluation showed more height deficiency than weight deficiency. Laboratory tests showed elevation of hepatic transaminases (12/19), hypercolesterolemia (8/14), hyperuricemia (6/17) and hypoglycemia (6/20). Liver function was not compromised in most of the cases. The results of glucagon tolerance test were variable. The histoenzymology study performed in 15 patients revealed the following results: Type VI (liver phosphorylase deficiency) in seven, Type I (glucose-6-phosphatase deficiency) in two, Type IV (brancher enzyme) in one and no conclusion could be drawn in five patients. The finding of hypoglycemia in few cases of this study can be justified by the few number of glycogenosis Type I, probably due to the fact that this type is the most easily diagnosed, with less necessity of referring them to specialized centers.
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PMID:[Hepatic glycogenosis in childhood: clinical and laboratory findings in 20 patients]. 872 90

S 5627 is a synthetic analogue of chlorogenic acid. S 5627 is a potent linear competitive inhibitor of glucose 6-phosphate (Glc-6-P) hydrolysis by intact microsomes (Ki = 41 nM) but is without effect on the enzyme in detergent- or NH4OH-disrupted microsomes. 3H-S 5627 was synthesized and used as a ligand in binding studies directed at characterizing T1, the Glc-6-P transporter. Binding was evaluated using Ca2+-aggregated microsomes, which can be sedimented at low g forces. Aside from a modest reduction in K values for both substrate and S 5627, Ca2+ aggregation had no effect on glucose-6-phosphatase (Glc-6-Pase). Scatchard plots of binding data are readily fit to a simple "two-site" model, with Kd = 21 nM for the high affinity site and Kd = 2 microM for the low affinity site. Binding to the high affinity site was competitively blocked by Glc-6-P (Ki = 9 microM), whereas binding was unaffected by mannose-6-phosphate, Pi, and PPi and only modestly depressed by 2-deoxy-D-glucose 6-phosphate, a poor substrate for Glc-6-Pase in intact microsomes. Thus the high affinity 3H-S 5627 binding site fits the criteria for T1. Permeabilization of the membrane with 0.3% (3-[(chloramidopropyl)-dimethylammonio]-1-propanesulfonate) activated Glc-6-Pase and broadened its substrate specificity, but it did not significantly alter the binding of 3H-S 5627 to the high affinity sites or the ability of Glc-6-P to block binding. These data demonstrate unequivocally that two independent Glc-6-P binding sites are involved in the hydrolysis of Glc-6-P by intact microsomes. The present findings are the strongest and most direct evidence to date against the notion that the substrate specificity and the intrinsic activity of Glc-6-Pase in native membranes are determined by specific conformational constraints imposed on the enzyme protein. These data constitute compelling evidence for the role of T1 in Glc-6-Pase activity.
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PMID:Direct evidence for the involvement of two glucose 6-phosphate-binding sites in the glucose-6-phosphatase activity of intact liver microsomes. Characterization of T1, the microsomal glucose 6-phosphate transport protein by a direct binding assay. 949 46

Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive disorder of glycogen metabolism caused by glucose-6-phosphatase (G6Pase) deficiency. It is characterized by short stature, hepatomegaly, hypoglycemia, hyperuricemia, and lactic acidemia. Various mutations have been reported in the G6Pase gene (G6PC). However, in Japanese patients, a g727t substitution was found to be the major cause of GSD-Ia, accounting for 20 of 22 mutant alleles [Kajihara et al., 1995], and no other mutations have been found in this population. We analyzed four Japanese GSD-Ia patients and identified three other mutations in addition to the g727t. They included two missense mutations (R83H and P257L) and one nonsense mutation (R170X). Each of the three mutations exhibited markedly decreased G6Pase activity when expressed in COS7 cells. A patient homozygous for R170X showed multiple episodes of profound hypoglycemia associated with convulsions, while P257L was associated with a mild clinical phenotype. The presence of R170X in three unrelated families may implicate that it is another important mutation in the etiology of GSD-Ia in Japanese patients. Thus, the detection of non-g727t mutations is also important in establishing the DNA-based diagnosis of GSD-Ia in this population.
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PMID:Heterogeneous mutations in the glucose-6-phosphatase gene in Japanese patients with glycogen storage disease type Ia. 1079 30