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)

A 4-year-old German girl was diagnosed as having glycogen storage disease type la and showed no other marked symptoms except hepatomegaly. The glucose-6-phosphatase activity in the liver was approximately 1.5% to 5.0% of normal values, and molecular analysis revealed compound heterozygosity for R83C and the novel mutation N264K. This result indicates that there is a wide clinical variation of glucose-6-phosphatase deficiency. DNA analysis is helpful for confirmation of the diagnosis, as well as establishment of the genotype and phenotype correlation in glycogen storage disease type 1a.
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PMID:A new mutation of the glucose-6-phosphatase gene in a 4-year-old girl with oligosymptomatic glycogen storage disease type 1a. 950 59

Glycogen storage disease type la (GSD1a) is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase (G6Pase). We analyzed the G6Pase genes of two unrelated Chinese families with GSD1a. DNA sequencing of all five exons and the exon-intron boundaries revealed a G T transversion at nucleotide 727 (727G-->T) in exon 5, which has previously been reported to cause abnormal splicing. In one family, the subject and her affected sister were confirmed to be homozygous for this mutation and their parents to be heterozygotes. In the other family, the proband was identified to be heterozygous for this mutation, and a novel mutation, the 341delG in exon 2, was identified. This mutation alters the reading frame and creates a stop codon TAA 15 codons downstream from the mutation, resulting in a truncated protein. Family studies revealed that the father was heterozygous for the 727G-->T mutation and that the mother was heterozygous for the 341delG mutation. This is the first time that the 727G T mutation has been found in Chinese patients or outside Japan. Since we only tested two GSD1a families and found 727G-->T in both, we believe that this mutation may also be prevalent in our local Chinese population. To investigate allele frequencies, we screened 385 Chinese healthy volunteers and found two asymptomatic carriers. Our findings suggest that the 727G-->T mutation is indeed prevalent in Hong Kong.
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PMID:Glucose-6-phosphatase gene (727G-->T) splicing mutation is prevalent in Hong Kong Chinese patients with glycogen storage disease type 1a. 963 72

Glycogen storage disease type Ia (GSD Ia) is an autosomal recessive condition, caused by a deficiency of hepatic glucose-6-phosphatase (G6Pase) activity. In a consanguineous family originating from northern Africa whose first daughter was affected with GSD Ia, we were able to identify the disease-causing mutation, a cytosine to thymine substitution at nucleotide 326 in exon 2 of the G6Pase gene (R83C). This mutation causes the disappearance of an HgaI site, and is thus easily detectable by restriction enzyme digestion. Both parents were heterozygous for this mutation. During the third pregnancy, fetal genomic DNA was extracted from a chorionic villus biopsy sampled at the 24th week of gestation. Exons 2 of the G6Pase gene were amplified by the polymerase chain reaction followed by HgaI digestion. Fetal DNA analysis indicated that the fetus had received both normal G6Pase alleles. This result was confirmed after birth. DNA analysis is the only reliable method for prenatal diagnosis of GSD Ia.
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PMID:Prenatal diagnosis of glycogen storage disease type Ia by restriction enzyme digestion. 966 12

Glycogen-storage diseases type I (GSD type I) are due to a deficiency in glucose-6-phosphatase, an enzymatic system present in the endoplasmic reticulum that plays a crucial role in blood glucose homeostasis. Unlike GSD type Ia, types Ib and Ic are not due to mutations in the phosphohydrolase gene and are clinically characterized by the presence of associated neutropenia and neutrophil dysfunction. Biochemical evidence indicates the presence of a defect in glucose-6-phosphate (GSD type Ib) or inorganic phosphate (Pi) (GSD type Ic) transport in the microsomes. We have recently cloned a cDNA encoding a putative glucose-6-phosphate translocase. We have now localized the corresponding gene on chromosome 11q23, the region where GSD types Ib and Ic have been mapped. Using SSCP analysis and sequencing, we have screened this gene, for mutations in genomic DNA, from patients from 22 different families who have GSD types Ib and Ic. Of 20 mutations found, 11 result in truncated proteins that are probably nonfunctional. Most other mutations result in substitutions of conserved or semiconserved residues. The two most common mutations (Gly339Cys and 1211-1212 delCT) together constitute approximately 40% of the disease alleles. The fact that the same mutations are found in GSD types Ib and Ic could indicate either that Pi and glucose-6-phosphate are transported in microsomes by the same transporter or that the biochemical assays used to differentiate Pi and glucose-6-phosphate transport defects are not reliable.
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PMID:A gene on chromosome 11q23 coding for a putative glucose- 6-phosphate translocase is mutated in glycogen-storage disease types Ib and Ic. 975 26

Glycogen storage disease type Ia (GSDIa), also known as von Gierke disease, is the most common and severe disease of glycogenoses and is caused by a deficiency of glucose-6-phosphatase (G6Pase) and transmitted by an autosomal recessive trait. The encoding gene of G6Pase is composed of only five exons and each exon is short. With heteroduplex analysis (HDA) method, we analyzed the genomic DNA from a patient diagnosed with GSDIa and from her parents. Exons II and IV of the patient showed heteroduplex bands. The mother had a heteroduplex band of exon II, and the father had a heteroduplex band of exon IV. In a mini-slab electrophoresis, exons II and IV of the patient did not show clear heteroduplex bands, but they appeared broader than the others, which made us suspect that they were heteroduplex bands. HDA is an easy and simple method and can verify mutant homozygous DNA fragments by adding wild-type DNA. We think that HDA may be a very useful screening method for the detection of novel genomic mutation in GSDIa in large-scale and mini-slab electrophoresis.
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PMID:Heteroduplex analysis: a useful screening method for glycogen storage disease type Ia. 978 10

The liver contains hepatocytes with varying ploidy and gene expression. To isolate cells on the basis of ploidy for analyzing mechanisms concerning cell proliferation and differentiation, we used Percoll gradients to separate F344 rat hepatocyte subpopulations. Specific fractions were enriched in polyploid (H2 fraction) or diploid (H3 and H4 fractions) hepatocytes containing glycogen and glucose-6-phosphatase. H4 cells were relatively smaller with greater nuclear/cytoplasmic ratios, less complex cytoplasm, and higher serum albumin or ceruloplasmin biosynthetic rates. H2 fraction cells were larger with lesser nuclear/cytoplasmic ratio, more complex cytoplasm, and more cytochrome P450 activity. Phenotypic marking showed that H4 cells originated in zone one and H2 cells in zones two or three of the liver lobule. H4 cells showed much greater mitogenic responsiveness to human hepatocyte growth factor. Retroviral gene transfer, which requires both viral receptors and cellular DNA synthesis, was significantly more efficient in H4 cells. The findings indicated that small diploid and large polyploid hepatocytes show unique biological differences. The ability to isolate hepatocytes of varying maturity is relevant for mechanisms concerning liver growth control and hepatic gene expression.
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PMID:Fractionation of rat hepatocyte subpopulations with varying metabolic potential, proliferative capacity, and retroviral gene transfer efficiency. 980 91

Deficiency of glucose-6-phosphatase (G6Pase), a key enzyme in glucose homeostasis, causes glycogen storage disease type 1a (GSD-1a), also know as von Gierke disease. Expression of the G6Pase gene is regulated by multiple hormones, including glucocorticoids. The synthetic glucocorticoid dexamethasone increased G6Pase mRNA abundance and gene transcription in H4-IIE hepatoma cells. Transient transfection assays demonstrated that the G6Pase promoter was active in H4-IIE cells only in the presence of dexamethasone. The minimal G6Pase promoter was contained within nucleotides -234/+3, which has two putative glucocorticoid response elements (GREs) at nucleotides -178/-164 (site 1) and -154/-140 (site 2). Electromobility shift and transient transfection assays showed that only GRE site 1 was required for glucocorticoid-activated transcription from the G6Pase promoter. Deletion analysis demonstrated that the DNA elements absolutely essential for glucocorticoid-stimulated transcription from the G6Pase promoter were contained within nucleotides -234/-212, encompassing binding motifs for hepatocyte nuclear factors (HNFs) 1 (-226/-212) and 4 (-231/-220). Electromobility shift and cotransfection assays showed that HNF1alpha bound to its cognate site and mediated transcription activation of the G6Pase gene by glucocorticoids.
DNA Cell Biol 1998 Nov
PMID:Hepatocyte nuclear factor 1alpha is an accessory factor required for activation of glucose-6-phosphatase gene transcription by glucocorticoids. 983 6

The use of in vitro systems in the assessment of xenobiotic metabolism has distinct advantages and disadvantages. While isolated hepatocytes and microsomes prepared from human liver may be used to generate data for comparisons among species and in vitro systems, such comparisons are generally performed on the basis of microsomal protein or million (viable) hepatocytes. Recently, in vitro data have been investigated for their value as quantitative predictors of in vivo metabolic capacity. Because of the existence of large amounts of trichloroethylene (TRI) data in the human, we have examined the metabolism of TRI as a case study in the development of a method to compare metabolism across species using in vitro systems and for extrapolation of metabolic rates from in vitro to in vivo. TRI is well metabolized by human hepatocytes in culture with a K(m) of 266 +/- 202 ppm (mean +/- SD) in headspace and a Vmax of 16.1 +/- 12.9 nmol/h/10(6) viable hepatocytes. We determined that human liver contains approximately 116 x 10(6) hepatocytes and 20.8 mg microsomal protein/g, based on DNA recovery and glucose-6-phosphatase activity, respectively. Thus, the microsomal protein content of hepatocytes is 179 micrograms microsomal protein/10(6) isolated hepatocytes. The microsomal apparent Vmax value of 1589 pmol/min/mg microsomal protein extrapolates to 17.07 nmol/h/10(6) hepatocytes. The combination of protein recovery and metabolic rate predicted a Vmax of approximately 1400 nmol/h/g human liver, which, when extrapolated and incorporated into an existing physiologically based pharmacokinetic (PBPK) model for TRI, slightly underpredicted TRI metabolism in the intact human. The quantitation, extrapolation, and inclusion of extrahepatic and cytochrome P450 (CYP)-independent TRI metabolism may increase the predictive value of this approach.
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PMID:In vitro to in vivo extrapolation for trichloroethylene metabolism in humans. 985 6

Type Ia glycogen storage disease (GSD1a) is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase (G6Pase). Recent cloning of the G6Pase gene and the subsequent identification of several disease-causing mutations have shown an ethnic molecular heterogeneity. Using SSCP analysis and DNA sequencing, we characterized the G6Pase gene of 53 unrelated Italian patients. The two most common mutations, R83C and Q347X, accounted for 66.9% of the mutant alleles. Eight novel mutations and three rare mutations were identified in 15.7% of disease alleles. These results suggest that a DNA-based method can be used as an initial screening in Italian patients clinically suspected of having GSD1a, avoiding liver biopsy for enzymatic diagnosis. In particular, a noninvasive diagnosis is a suitable method for the Italian subpopulation coming from Sicily, where the R83C mutation is present in 80% of mutant alleles. Molecular carrier detection and prenatal diagnosis can be provided to GSD1a families with identified mutation in the propositus.
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PMID:Mutations in the glucose-6-phosphatase gene of 53 Italian patients with glycogen storage disease type Ia. 1007 Jun 17

In liver and kidney, the terminal step in the gluconeogenic pathway is catalyzed by glucose-6-phosphatase (G-6-Pase). This enzyme is actually a multicomponent system, the catalytic subunit of which was recently cloned. Numerous reports have also described the presence of G-6-Pase activity in islets, although the role of G-6-Pase in this tissue is unclear. Arden and associates have described the cloning of a novel cDNA that encodes an islet-specific G-6-Pase catalytic subunit-related protein (IGRP) (Arden SD, Zahn T, Steegers S, Webb S, Bergman B, O'Brien RM, Hutton JC: Molecular cloning of a pancreatic islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP). Diabetes 48:531-542, 1999). We screened a mouse BAC library with this cDNA to isolate the IGRP gene, which spans approximately 8 kbp of genomic DNA. The exon/intron structure of the IGRP gene has been mapped and, as with the gene encoding the liver/kidney G-6-Pase catalytic subunit, it is composed of five exons. The sizes of these exons are 254 (I), 110 (II), 112 (III), 116 (IV), and 1284 (V) bp, similar to those of the G-6-Pase catalytic subunit gene. Two interspecific backcross DNA mapping panels were used to unambiguously localize the IGRP gene (map symbol G6pc-rs) to the proximal portion of mouse chromosome 2. The IGRP gene transcription start site was mapped by primer extension analysis, and the activity of the IGRP gene promoter was analyzed in both the islet-derived HIT cell line and the liver-derived HepG2 cell line. The IGRP and G-6-Pase catalytic subunit gene promoters show a reciprocal pattern of activity, with the IGRP promoter being approximately 150-fold more active than the G-6-Pase promoter in HIT cells.
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PMID:Structure and promoter activity of an islet-specific glucose-6-phosphatase catalytic subunit-related gene. 1007 54


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