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

UDP-glucuronosyltransferase (UDPGT) was studied immunohistochemically in hepatic foci and nodules of N-nitrosomorpholine-treated mice. Serial sections were stained for glucose-6-phosphatase (G6Pase). It was found that a high percentage of G6Pase-negative liver foci and nodules were also UDPGT-negative (34%). In addition, G6Pase-negative foci without altered UDPGT phenotype (30%) and UDPGT-negative foci without altered G6Pase phenotype (8%) were detected. G6Pase-positive foci were also present (24%). Interestingly, most G6Pase-positive foci were UDPGT-positive (16%). Some G6Pase-positive lesions without altered UDPGT phenotype were also found (8%). The major phenotype observed in rat hepatocarcinogenesis models (UDPGT-positive/G6Pase-negative foci) was not detectable in the mouse model. These results demonstrate heterogeneous alterations of UDPGTs in mouse hepatic foci. They furthermore suggest marked differences between the mouse and the rat in the regulation of UDPGTs in similarly induced rat hepatic foci.
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PMID:Heterogeneous alterations of UDP-glucuronosyltransferases in mouse hepatic foci. 254 57

We have studied the effects of prochlorperazine on the activities of UDP-glucuronosyltransferase and glucose-6-phosphatase (glucose-6-P'ase) in rat liver microsomes. The activity of UDP-glucuronosyltransferase was increased in a graded fashion by addition of prochlorperazine. Maximal stimulation occurred at 1 mg prochlorperazine to 2 mg microsomal protein, which resulted in a 6-fold increase in activity. However, with smaller concentrations of drug, there was a time-dependent increase in the activity of UDP-glucuronosyltransferase. Sensitivity of UDP-glucuronosyltransferase to activation by UDP-N-acetylglucosamine was lost after treatment of microsomes with prochlorperazine. These results indicate that prochlorperazine causes a profound reorganization of the interactions between lipids and enzyme since the activity and allosteric properties of UDP-glucuronosyltransferase are known to depend on interactions with lipids in a gel phase. Glucose-6-P'ase also was activated in a graded fashion by prochlorperazine; 1 mg of drug/2 mg microsomal protein resulted in a 60% increase in activity. The temperature-dependent instability of glucose-6-P'ase was increased by treatment of microsomes with prochlorperazine and could be prevented only partially by substrate. We conclude that prochlorperazine disrupts the structural organization between lipids and proteins in microsomal membranes, altering thereby the activity and regulation of at least two different integral membrane proteins.
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PMID:Effects of prochlorperazine on the function of integral membrane proteins. 283 74

Specific activities of UDP-glucuronosyltransferase and glucose-6-phosphatase, a marker enzyme of endoplasmic reticulum, were measured in mitochondria and microsomes. In mitochondria the specific activity of UDP-glucuronosyltransferase represented only 7-11% of that found in microsomes, when measured in the presence of various aglycone substrates, including 4-nitrophenol, 4-methylumbelliferone, 1-naphthol, phenolphthalein, testosterone and 17 beta-estradiol. Similarly, the specific activity of glucose-6-phosphatase in mitochondrial preparations was about 80% of that found in microsomes. In conclusion, it seems that in rat liver the UDP-glucuronosyltransferase activity associated with mitochondrial fractions reflects the presence of membrane fragments derived from endoplasmic reticulum, rather than mitochondrial location of this enzyme.
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PMID:Re-investigation of the presence of UDP-glucuronosyltransferase in rat liver mitochondria. 629 Nov 11

Histone 2A increases glucose-6-phosphatase activity in liver microsomes. The effect has been attributed either to the conformational change of the enzyme, or to the permeabilization of microsomal membrane that allows the free access of substrate to the intraluminal glucose-6-phosphatase catalytic site. The aim of the present study was the critical reinvestigation of the mechanism of action of histone 2A. It has been found that the dose-effect curve of histone 2A is different from that of detergents and resembles that of the pore-forming alamethicin. Inhibitory effects of EGTA on glucose-6-phosphatase activity previously reported in histone 2A-treated microsomes have been also found in alamethicin-permeabilized vesicles. The effect of EGTA cannot therefore simply be an antagonization of the effect of histone 2A. Histone 2A stimulates the activity of another latent microsomal enzyme, UDP-glucuronosyltransferase, which has an intraluminal catalytic site. Finally, histone 2A renders microsomal vesicles permeable to non-permeant compounds. Taken together, the results demonstrate that histone 2A stimulates glucose-6-phosphatase activity by permeabilizing the microsomal membrane.
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PMID:Histone 2A stimulates glucose-6-phosphatase activity by permeabilization of liver microsomes. 1209 38

Contribution of translocon peptide channels to the permeation of low molecular mass anions was investigated in rat liver microsomes. Puromycin, which purges translocon pores of nascent polypeptides, creating additional empty pores, raised the microsomal uptake of radiolabeled UDP-glucuronic acid, while it did not increase the uptake of glucose-6-phosphate or glutathione. The role of translocon pores in the transport of small anions was also investigated by measuring the effect of puromycin on the activity of microsomal enzymes with intraluminal active sites. The mannose-6-phosphatase activity of glucose-6-phosphatase and the activity of UDP-glucuronosyltransferase were elevated upon addition of puromycin, but glucose-6-phosphatase and beta-glucuronidase activities were not changed. The increase in enzyme activities was due to a better access of the substrates to the luminal compartment rather than to activation of the enzymes. Antibody against Sec61 translocon component decreased the activity of UDP-glucuronosyltransferase and antagonized the effect of puromycin. Similarly, the addition of the puromycin antagonist anisomycin or treatments of microsomes, resulting in the release of attached ribosomes, prevented the puromycin-dependent increase in the activity. Mannose-6-phosphatase and UDP-glucuronosyltransferase activities of smooth microsomal vesicles showed higher basal latencies that were not affected by puromycin. In conclusion, translationally inactive, ribosome-bound translocons allow small anions to cross the endoplasmic reticulum membrane. This pathway can contribute to the nonspecific substrate supply of enzymes with intraluminal active centers.
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PMID:Translocon pores in the endoplasmic reticulum are permeable to small anions. 1661 37

We have previously achieved a high level of long-term liver replacement by transplanting freshly isolated embryonic day (ED) 14 rat fetal liver stem/progenitor cells (FLSPCs). However, for most clinical applications, it will be necessary to use cryopreserved cells that can effectively repopulate the host organ. In the present study, we report the growth and gene expression properties in culture of rat FLSPCs cryopreserved for up to 20 months and the ability of cryopreserved FLSPCs to repopulate the normal adult rat liver. After thawing and placement in culture, cryopreserved FLSPCs exhibited a high proliferation rate: 49.7% Ki-67-positive on day 1 and 34.7% Ki-67-positive on day 5. The majority of cells were also positive for both alpha-fetoprotein and cytokeratin-19 (potentially bipotent) on day 5. More than 80% of cultured cells expressed albumin, the asialoglycoprotein receptor, and UDP-glucuronosyltransferase (unique hepatocyte-specific functions). Expression of glucose-6-phosphatase, carbamyl phosphate synthetase 1, hepatocyte nuclear factor 4alpha, tyrosine aminotransferase, and oncostatin M receptor mRNAs was initially negative, but all were expressed on day 5 in culture. After transplantation into the normal adult rat liver, cryopreserved FLSPCs proliferated continuously, regenerated both hepatocytes and bile ducts, and produced up to 15.1% (mean, 12.0% +/- 2.0%) replacement of total liver mass at 6 months after cell transplantation. These results were obtained in a normal liver background under nonselective conditions. This study is the first to show a high level of long-term liver replacement with cryopreserved fetal liver cells, an essential requirement for future clinical applications.
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PMID:Properties of cryopreserved fetal liver stem/progenitor cells that exhibit long-term repopulation of the normal rat liver. 1677 53

In toxicological research, immortalized human hepatocytes provide a useful alternative to primary hepatocytes because interindividual variability in the expression of drug-metabolizing enzymes and drug transporters can largely be eliminated. However, it is essential that the cell line retain the original phenotype. The purpose of this study was to characterize a novel spontaneously immortalized human hepatocyte cell line, HC-04, with respect to the transcript and functional protein expression profile for the major drug-metabolizing enzymes and transmembrane transporters. HC-04 cells retained hepatocyte-specific function including albumin production and ornithine transcarbamoylase and glucose-6-phosphatase activity. Most of the major CYP forms were expressed at basal levels and responsive to inducing agents. In particular, CYP3A4 was expressed abundantly, and HC-04 cells were able to metabolize the CYP3A4 probe, midazolam, at a rate similar to primary human hepatocytes. Furthermore, the major human sulfotransferase and UDP-glucuronosyltransferase forms, as well as members of the ABC and SLC transporter superfamilies, nuclear receptors, and hepatic transcription factors were also expressed. HC-04 cells readily responded to standard hepatotoxicants that are dependent on CYP-mediated bioactivation, while another, tumor-derived cell line remained refractory to the drug challenge. Collectively, HC-04 cells provide a reliable, stable, and reproducible model for biomechanistic studies in drug toxicology.
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PMID:Molecular and functional characterization of drug-metabolizing enzymes and transporter expression in the novel spontaneously immortalized human hepatocyte line HC-04. 1759 Mar 8