Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

We have utilized S-farnesyl-Leu-Ala-Arg-Tyr-Lys-Cys as a methyl-accepting substrate to characterize a membrane-bound C-terminal protein methyltransferase from rat liver. We have localized the activity to the microsomal fraction and show that the bulk of the enzyme fractionates by density gradient centrifugation with glucose-6-phosphatase, a marker of the endoplasmic reticulum, and not with 5'-nucleotidase, a marker of the plasma membrane, or galactosyl:N-acetylglucosamine transferase, a marker of the Golgi apparatus. This methyltransferase appears to form an integral part of the membrane structure. Its activity is markedly affected by a variety of detergents used to solubilize membrane proteins in their native form. All activity is lost when membranes are treated with seven different detergents at a concentration of 1% (w/v). The activity is inhibited by N-ethylmaleimide, although it can be protected against inactivation with its substrate S-adenosyl-L-methionine, or its product S-adenosyl-L-homocysteine. Finally, we find that 5'-methylthioadenosine, a substrate analogue reported to be an inhibitor of this activity in other studies, is not an effective inhibitor in vitro.
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PMID:Characterization of a rat liver protein carboxyl methyltransferase involved in the maturation of proteins with the -CXXX C-terminal sequence motif. 132 16

Twenty-four male (12 obese and 12 lean) and 21 female (11 obese and 10 lean) SHR/N-cp rats were fed a diet containing either 54% sucrose or starch for periods of 3-4 months. Rats were killed after a 14-16 h fast and liver enzyme activities were determined in both sex groups. Liver glucose-6-phosphatase (G6Pase), fructose 1,6-bisphosphatase (FBPase), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), malic enzyme (ME), phosphofructokinase (PFK), glucokinase (GK), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels (per total liver capacity) were significantly affected by phenotype (obese > lean). Arginase and ornithine transcarbamylase levels were analysed only in male rats and were found to be elevated in obese rats as compared to lean littermates. Some of the above changes in enzyme levels were exaggerated by sucrose feeding but not the changes in FBPase, PEPCK, ME and GK (in both sexes) plus AST, arginase and arginine synthase activities in male rats and ALT levels in female rats. Results from SHR/N-cp rats published in this paper were compared to results obtained from LA/N-cp rats published previously. Comparison of the non-diabetic obese LA/N-cp with the diabetic obese SHR/N-cp male shows a greater excess in lipogenic capacity of the liver in the LA/N-cp male rat. The SHR/N-cp obese female also shows a greater liver lipogenic capacity as compared with the obese male SHR/N-cp rat. The results suggest that an adaptation of excessive lipogenesis in the liver of obese rats may be an anti-diabetogenic adaptation resulting in increased glucose conversion to lipids, thus reducing blood glucose levels.
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PMID:Adaptation in enzyme (metabolic) pathways to obesity, carbohydrate diet and to the occurrence of NIDDM in male and female SHR/N-cp rats. 133 Sep 56

Normoglycemic ob/ob mice were treated for 24 or 48 h with either 25 micrograms/day of dexamethasone or saline. After an overnight fast, the animals were killed and pancreatic islets were incubated with 3H2O or [U-14C]glucose or [5-3H]glucose at 5.5 and 16.7 mM glucose. Incorporation of 3H from 3H2O into carbon 2 of medium glucose and the yield of 14CO2 from [U-14C]glucose and 3H2O from [5-3H]glucose were measured. Dexamethasone treatment for 48 h significantly increased the rate of dephosphorylation of glucose in islets both at 5.5 mM (24 vs. 16%) and 16.7 mM (56 vs. 36%) glucose, whereas glucose oxidation and utilization were unaffected. Dexamethasone treatment also inhibited insulin release by approximately 60% at 5.5 and 16.7 mM glucose, either in the presence or absence of 10 mM arginine, but had no effect when insulin release was stimulated by 1 mM 3-isobutyl-1-methylxanthine. Moreover, 24-h treatment with dexamethasone significantly increased glucose cycling at low and high glucose concentrations in the medium and inhibited insulin responsiveness to glucose and arginine. In conclusion, short-term dexamethasone treatment increases glucose flux through glucose-6-phosphatase in islets from ob/ob mice. This effect may contribute to the decreased insulin response to glucose and arginine found in animals treated with dexamethasone.
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PMID:Glucocorticoid increases glucose cycling and inhibits insulin release in pancreatic islets of ob/ob mice. 138 56

Twenty obese and 20 lean LA/N-cp male rats and 20 male Sprague-Dawley rats were fed a diet containing either 54 percent sucrose or starch for six weeks. After a 14-16 hour fast, rats were killed. Liver and kidney enzyme activities were determined in the LA/N-cp rats while plasma urea and selected amino acids were determined in all rats. Liver glucose-6-phosphatase (G6PASE), fructose-1,6-bisphosphatase (FBPASE), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), malic enzyme (ME), glucokinase (GK), pyruvate kinase (PK), phosphofructokinase (PFK), glutamic-oxaloacetic-transaminase (GOT), glutamic-pyruvic transaminase (GPT), arginase (ARGASE), arginine-synthase (ARG-SYN) and ornithine transcarbamylase (OTC) levels were significantly affected by phenotype (obese greater than lean). All the above changes in enzyme levels were exaggerated by sucrose-feeding with the exception of PK, PFK, GOT, GPT, ARGASE and ARG-SYN. Kidney cortex G6PASE, PEPCK and ARGASE activities were higher in the obese rats as compared to the lean littermates. Sucrose feeding resulted in higher cortex G6PASE, FBPASE and PEPCK as compared to starch-fed rats. A phenotype effect was noted with plasma glutamate, urea, leucine, isoleucine and valine (obese greater than lean) and a diet effect was seen with aspartate, phenylalanine, leucine and valine (sucrose greater than starch) concentration. Sprague-Dawley rats had higher plasma urea and lower alanine than lean LA/N-cp males. Metabolic obesity in the LA/N-cp rat appears to involve an elevated capacity for pathways of glycolysis, gluconeogensis, lipogenesis and amino acid catabolism in the liver.
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PMID:Effect of dietary carbohydrate on liver and kidney enzyme activities and plasma amino acids in the LA/N-cp rat. 204 12

1. The rat kidney kininogenase (KGA) activity was located mainly in the kidney cortex.2. Differential centrifugation of kidney cortex homogenate revealed that the microsomal fraction contained more KGA activity per unit of protein than the other subcellular fractions.3. Subfractionation of the microsomal fraction showed that the KGA activity was recovered in a subfraction also containing high specific activity of both alkaline phosphate and glucose-6-phosphatase. It is suggested that the KGA activity is localized in the plasma membrane and/or endoplasmic reticulum membranes of kidney cortical cells.4. Hydrolysis of N-alpha-benzoyl-L-arginine ethyl ester at pH 8.5 paralleled the KGA activity.
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PMID:Localization of kininogenase in the rat kidney. 431 91

Two SH-dependent proteinases (I and II) active in neutral media were isolated from bovine spleen and purified to apparent homogeneity. The histone-hydrolyzing activity of proteinase I was increased 3500-fold as compared to that of the original extract. Proteinase I hydrolyzed a variety of proteins (histones, azocasein, hemoglobin, collagen) but did not hydrolyze low molecular weight synthetic substrates, such as BAPA, BANA, BAEE, ATEE, Leu-beta-NA, Arg-beta-Na and Ala-beta-NA. The molecular weight of the enzyme as determined by SDS electrophoresis was found to be about 23,000. Isoelectrofocusing of the enzyme resulted in one major component with pI of 6.05 and in two minor components with pI of 6.2 and 6.4. Proteinase II hydrolyzed Leu-beta-NA, Arg-beta-NA and Ala-beta-NA but did not hydrolyze beta-naphthylamides of dicarboxylic acids and Gly-Phe-beta-Na. This proteinase split BANA and histone and very slowly split azocasein and collagen. Proteinase II was found to have a molecular weight of 30 000 and a pI of 6.8-6.9. Proteinase I inactivated fructose-1.6-diphosphate aldolase, partly inactivated glucose-6-phosphatase dehydrogenase and caused activation of phosphodiesterase of cyclic nucleotides. Proteinase II had no effect on the activity of the above enzymes. A comparison of proteinase I and II with enzymes described in literature demonstrated that the former was cathepsin L, while the latter was cathepsin H from spleen.
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PMID:[Characteristics of two thiol proteinases from spleen active in neutral media]. 675 12

Glycogen storage disease type 1a (GSD 1a), an autosomal recessive disease, is caused by the inactivity of glucose-6-phosphatase, the gene of which has been recently cloned. We report on the missense mutation C-->T at nucleotide 326 of the G6Pase gene, causing the change of the Arg codon at position 83 into a Cys codon, as the single mutation detected in six Jewish patients. This finding suggests that this mutation might be prevalent among the Jewish population. A new missense mutation T-->G at nucleotide 576 resulting in V166G was found in an Arab Muslim patient. These families may benefit now from pre- and postnatal diagnosis by analysis of DNA from blood and amniotic fluid or chorionic villus cells rather than liver biopsy. No mutations in the G6Pase gene were detected in two GSD 1b patients.
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PMID:Characterization of the mutations in the glucose-6-phosphatase gene in Israeli patients with glycogen storage disease type 1a: R83C in six Jews and a novel V166G mutation in a Muslim Arab. 762 38

Glycogen storage disease (GSD) type 1, which is caused by the deficiency of glucose-6-phosphatase (G6Pase), is an autosomal recessive disease with heterogenous symptoms. Two models of G6Pase catalysis have been proposed to explain the observed heterogeneities. The translocase-catalytic unit model proposes that five GSD type 1 subgroups exist which correspond to defects in the G6Pase catalytic unit (1a), a stabilizing protein (1aSP), the glucose-6-P (1b), phosphate/pyrophosphate (1c), and glucose (1d) translocases. Conversely, the conformation-substrate-transport model suggests that G6Pase is a single multifunctional membrane channel protein possessing both catalytic and substrate (or product) transport activities. We have recently demonstrated that mutations in the G6Pase catalytic unit cause GSD type 1a. To elucidate whether mutations in the G6Pase gene are responsible for other GSD type 1 subgroups, we characterized the G6Pase gene of GSD type 1b, 1c, and 1aSP patients. Our results show that the G6Pase gene of GSD type 1b and 1c patients is normal, consistent with the translocase-catalytic unit model of G6Pase catalysis. However, a mutation in exon 2 that converts an Arg at codon 83 to a Cys (R83C) was identified in both G6Pase alleles of the type 1aSP patient. The R83C mutation was also demonstrated in one homozygous and five heterogenous GSD type 1a patients, indicating that type 1aSP is a misclassification of GSD type 1a. We have also analyzed the G6Pase gene of seven additional type 1a patients and uncovered two new mutations that cause GSD type 1a.
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PMID:Mutations in the glucose-6-phosphatase gene are associated with glycogen storage disease types 1a and 1aSP but not 1b and 1c. 781 21

Glycogen storage disease (GSD) type 1a is an autosomal recessive inborn error of metabolism caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. Southern blot hybridization analysis using a panel of human-hamster hybrids showed that human G6Pase is a single-copy gene located on chromosome 17. To correlate specific defects with clinical manifestations of this disorder, we identified mutations in the G6Pase gene of GSD type 1a patients. In the G6Pase gene of a compound heterozygous patient (LLP), two mutations in exon 2 of one allele and exon 5 of the other allele were identified. The exon 2 mutation converts an arginine at codon 83 to a cysteine (R83C). This mutation, previously identified by us in another GSD type 1a patient, was shown to have no detectable phosphohydrolase activity. The exon 5 mutation in the G6Pase gene of LLP converts a glutamine codon at 347 to a stop (Q347SP). This Q347SP mutation was also detected in all exon 5 subclones (five for each patient) of two homozygous patients, KB and CB, siblings of the same parents. The predicted Q347SP mutant G6Pase is a truncated protein of 346 amino acids, 11 amino acids shorter than the wild type G6Pase of 357 residues. Site-directed mutagenesis and transient expression assays demonstrated that G6Pase-Q347SP was devoid of G6Pase activity. G6Pase is an endoplasmic reticulum (ER) membrane-associated protein containing an ER retention signal, two lysines (KK), located at residues 354 and 355. We showed that the G6Pase-K355SP mutant containing a lysine-355 to stop codon mutation is enzymatically active. Our data demonstrate that the ER protein retention signal in human G6Pase is not essential for activity. However, residues 347-354 may be required for optimal G6Pase catalysis.
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PMID:Identification of mutations in the gene for glucose-6-phosphatase, the enzyme deficient in glycogen storage disease type 1a. 818 31

Hepatomas tend to have a decreased glucose-6-phosphatase activity. We have observed phenotypic stability for this change in Morris hepatomas transplanted in rats. To determine if this decrease is selective for translocase functions or the hydrolase activity associated with glucose-6-phosphatase, we have compared activities in liver and hepatomas with glucose-6-phosphate or mannose-6-phosphate as substrates and with intact or histone-disrupted microsomes. In five out of seven subcutaneously transplanted rat hepatoma lines, the microsomal mannose-6-phosphatase activity was lower than in preparations from liver of normal or tumor-bearing rats. With liver microsomes and with most hepatoma microsomes, preincubation with calf thymus histones caused a greater increase in mannose-6-phosphatase than in glucose-6-phosphatase activity. In studies with liver and hepatoma microsomes there were similar increases in mannose-6-phosphatase activity with total calf thymus histones and arginine-rich histones. A smaller increase was seen with lysine-rich histones. The effect of polylysine was similar to the action of lysine-rich histones. There was only a small effect with protamine at the same concentration (1 mg/ml). Rat liver or hepatoma H1 histones gave only about half the activation seen with core nucleosomal histones. Our data suggested that microsomes of rat hepatomas tend to have decreased translocase and hydrolase functions of glucose-6-phosphatase relative to activities in untransformed liver.
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PMID:Changes in the glucose-6-phosphatase complex in hepatomas. 839 4


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