Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pyruvate, orthophosphate dikinase is a key enzyme in photosynthesis in some plants that exploit the C4 photosynthetic pathway for the fixation of CO2. The gene for this enzyme has been cloned and its primary structure has been analyzed. The sequence of the cloned genes spans about 12 kilobase pairs and consists of 19 exons. The site of initiation of transcription is located 211 nucleotides upstream from the first nucleotide of the initiation codon (position -211). Typical TATA and inverted CCAAT elements are present in the anticipated regions, as well as a sequence that is homologous to the binding site of Sp-1 protein (-51 to -42). Three long, direct-repeated sequences are present contiguously in the 5'-flanking region (-286 to -172), and two of the repeated sequences include sequences homologous to the core sequence of SV40 enhancer in the 3'-end portions. Southern blot analysis, coupled with mapping by analysis of restriction fragment length polymorphism, indicates that the gene for the enzyme involved in C4 photosynthesis is encoded by a single-copy gene and is located on chromosome 6. To test the promoter activity of the isolated gene, a chimeric gene composed of the 5'-flanking region of the gene and a structural gene for bacterial beta-glucuronidase was constructed and introduced into tobacco protoplasts by electroporation or used to transform tobacco plants by Agrobacterium-mediated transfer of the gene. In both cases, expression of the beta-glucuronidase gene was observed, indicating that the 5'-flanking region of the gene can act as a promoter in tobacco cells.
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PMID:Structure, genetic mapping, and expression of the gene for pyruvate, orthophosphate dikinase from maize. 217 Mar 54

In the dog, the major excretory metabolite of the antidepressant sertraline was characterized as sertraline carbamoyl-O-glucuronide. The intact conjugate was isolated from bile by HPLC. The metabolite was labile to beta-glucuronidase and produced sertraline as the single hydrolytic product, based on HPLC and GC-MS analyses. By fast atom bombardment MS analysis, [M+H]+ and [M+Na]+ ions at m/z 526 and 548 were observed, as were the proton and sodium adducts of the aglycone (m/z 350 and 372) due to cleavage of the glycosidic bond and elimination of the glucuronic acid moiety (176 amu). The observed mass of the aglycone was 44 amu greater than sertraline, indicating that a carbamic acid of this secondary amine was conjugated with glucuronic acid. These data suggest that sertraline in solution reversibly associates with CO2 before formation of sertraline carbamoyl-O-glucuronide. This novel amine glucuronide was also identified in human plasma after the oral administration of sertraline to each of seven subjects. The glucuronide was stable in plasma at both acidic and basic pH.
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PMID:Characterization of a carbamic acid ester glucuronide of the secondary amine sertraline. 256 71

A sensitive fluorimetric assay to determine both Phase 1 (oxidation) and Phase 2 (conjugation) drug metabolism in epidermal cells isolated from hairless mice, using ethoxycoumarin as a model substrate, is described. Ethoxycoumarin was metabolized by isolated epidermal cells via dealkylation to 7-hydroxycoumarin (7-OHC) and subsequent conjugation. Phase 1 metabolites were extracted in ether from the aqueous incubation media, back extracted into sodium hydroxide and determined fluorimetrically. Conjugated metabolites remaining in the aqueous phase were hydrolysed by the action of beta-glucuronidase and extracted and determined in a similar manner. The production of free 7-OHC by isolated epidermal cells was biphasic at all substrate concentrations tested, exhibiting an initial linear increase followed by a plateau phase. The plateau phase was attributable to the conjugation of 7-OHC produced in situ. Metabolism was inhibited by SKF 525A, carbon monoxide, and alpha-naphthoflavone. Endogenous supplies of reducing equivalents in the form of NADPH were adequate to attain maximal rates of metabolism. With human hair follicles both Phase 1 and Phase 2 activity was detectable in 7 out of 11 subjects. The assay has the advantages of being sensitive, producing single defined metabolites from both Phase 1 and Phase 2 metabolism; is readily adaptable to human skin samples.
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PMID:Phase 1 and Phase 2 drug metabolism in isolated epidermal cells from adult hairless mice and in whole human hair follicles. 405 99

Studies on the activity of the glucuronic acid pathway in alloxan diabetic rabbits were carried out. Amount of D-glucaric acid, L-ascorbic acid, and D-glucuronic acid in urine increased in the case of the alloxan diabetic rabbits. The transformation from D-glucuronolactone to D-glucaric acid was higher than normal in the diabetic animals. The expired 14-CO2 decreased and urinary excretion of labeled L-gulonic acid increased after administration of 6-14-C-glucuronolactone in the diabetic rabbits. L-Gulonic acid dehydrogenase, lactonase II, and beta-glucuronidase activities were reduced, and UDPGA-pyrophosphatase, D-glucuronic acid-1-phosphatase, and UDPGA-transferase activities increased in the diabetic rabbit liver. From these results, it may be concluded that an increase of endogenous D-glucuronic acid in the diabetic states could be attributed to a metabolid defect in the step of L-gulonic acid dehydrogenation and to the enhancement of UDPGA-pyrophosphatase and D-glucuronic acid-1-phosphate phosphatase activities.
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PMID:Glucuronic acid pathway in alloxan diabetic rabbits. (I). Urinary excretion of metabolites related to the glucuronic acid pathway. 446 73

Of patients with acute carbon monoxide poisoning admitted to the Trauma Intensive Care Unit of the Osaka University Hospital 39.5% (17/43) manifested hyperamylasemia. Iszyme studies in 16 such patients revealed 87.5% to be of the salivary type. Two patients presented with hyperamylasemia of the pancreatic-salivary type. There was no pancreatic type hyperamylasemia among these patients, negating the possible involvement of the pancreas in hyperamylasemia from carbon monoxide poisoning. There was a statistically significant difference in amylase levels between the arterial and the external jugular venous blood, indicating the salivary gland as the organ mainly responsible for hyperamylasemia in carbon monoxide poisoning. Amylase levels coincided well with the level of consciousness and the base excess. The amylase levels correlated significantly with beta-glucuronidase levels, suggesting the hyperpermeability of cell membranes of the salivary gland as the chief factor in hyperamylasemia secondary to acute carbon monoxide poisoning.
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PMID:Hyperamylasemia in acute carbon monoxide poisoning. 617 19

Whole isolated ellipsoids (sheathed capillaries of Schweiger-Seidel) of the pig spleen were explanted in Medium 199 containing 20% fetal calf serum or horse serum respectively. Cultures were kept in a gas phase of 5% carbon dioxide in air at 37 degrees C. After about 4 days in culture the outgrowth of two morphologically different cell types was apparent. Small cells of fusiform or stellate morphology displayed high activity of acid phosphatase. N-acetyl-beta-glucosaminidase and beta-glucuronidase activity were also detectable. Furthermore these cells were highly reactive for unspecific esterase and gamma-glutamyl transpeptidase activity. Endogenous peroxidase activity was present in the cytoplasm and in the perinuclear space. Stellate cells therefore are thought of as ellipsoid macrophages. Additional observations reported are the expression of Fc-receptors on stellate cells. They triggered the phagocytosis of opsonized test particles. The second cell type showed fibroblastic morphology. The large well spread cells did exhibit low activities of acid phosphatase and N-acetyl-beta-glucosaminidase. The other enzyme activities examined were not detectable. The nature of these cells is not well understood at present. Most likely they are constituents of the framework of the ellipsoids. No transitions between stellate cells and fibroblastic cells were found.
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PMID:Isolation, culture, and preliminary characterization of ellipsoids (sheathed capillaries of Schweigger-Seidel) of the pig spleen. II. An enzyme histochemical study of in vitro cultivated ellipsoids. 650 Sep 98

Peripheral blood monocytes isolated from patients with congenital hemolytic anemia, hereditary xerocytosis and spherocytosis, demonstrated in vivo engulfment of red cell and platelet fragments. In addition, morphometric studies performed on these monocytes showed an increase in cytoplasmic/nuclear ratio as well as lysosome and phagosome volumes. The production of carbon dioxide from glucose-1-14C in abnormal monocytes was increased (15-80%) but the intracellular values of beta-glucuronidase and esterase activity were similar to control monocytes. Monocyte locomotion assessed in the presence of chemotactic stimuli was found significantly increased (73 +/- 12 monocytes/oil immersion fields vs. 46 +/- 5 for control monocytes). We concluded that the monocytes in hemolytic anemias associated with increased in vitro red cell fragmentation have some features resembling the 'stimulated' monocytes and that this alteration may be due to red blood cell fragment ingestion.
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PMID:Characteristics of peripheral blood monocytes in hereditary xerocytosis and spherocytosis. 681 Jun 26

The metabolism of the antiarrhythmic drug tocainide (I) has been shown previously to occur via a novel pathway involving the addition of carbon dioxide to the primary amine nitrogen of I followed by conjugation with glucuronic acid. The product of this reaction, tocainide carbamoyl O-beta-D-glucuronide (II), the principal metabolite of I in humans, has been found to cyclize under strongly basic conditions to form 3-(2,6-xylyl)-5-methylhydantoin (III). Thus, evidence for the existence of II can be obtained by two different procedures: conversion of II to III in the presence of strong base and by hydrolysis of II with beta-glucuronidase. The principal purpose of the present investigation was to identify suitable species for studies of the mechanism involved in the formation of II, as well as to find an animal model suitable for toxicological evaluation of tocainide and structurally related compounds. Eight animal species were examined to identify those capable of metabolizing I into II. The fraction of an intraperitoneal dose excreted in urine as II was estimated by measurement of tocainide released by beta-glucuronidase mediated hydrolysis of urine and by the quantitation of III formed after alkalinization of urine samples. Urinary recovery of unchanged drug ranged from 9.5% of the dose in the gerbil to 48.7% in the cat. The percent of the dose excreted in urine as acid hydrolyzable conjugates ranged from less than 1% in the gerbil to a mean of 13% in the rabbit. Guinea pigs, dogs, cats, rabbits, and pigtail monkeys excreted amounts of II ranging from 0.2 to 2.4% of the dose. Thus, none of the species appeared to be a suitable model for the study of the mechanism of formation of II because of the quantitative insignificance of this pathway.
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PMID:Species differences in the urinary excretion of the novel primary amine conjugate: tocainide carbamoyl O-beta-D-glucuronide. 713 Dec 64

The metabolism of tocainide, an experimental antiarrhythmic drug, was studied in humans. Urinary excretion of unchanged drug was 28-55% in 24 hr after oral dosing. Urine hydrolysis with hydrochloric acid or beta-glucuronidase increased tocainide recovery to 55-79%. Saccharo-1,4-lactone inhibited the beta-glucuronidase-mediated tocainide recovery increase. Adjustment of urine to pH 13 produced a compound identified as 3-(2,6-xylyl)-5-methylhydantoin. Evidence suggests that it was derived from the same metabolite that formed the additional tocainide after acid or beta-glucuronidase treatment. Tocainide carbamoyl O-beta-D-glucuronide is the structure proposed for the metabolite. The suggested pathway for its formation involves the addition of carbon dioxide to the amino nitrogen of tocainide followed by uridine diphosphate-glucuronic acid conjugation.
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PMID:Tocainide conjugation in humans: novel biotransformation pathway for a primary amine. 735 40

Glycine decarboxylase is a mitochondrial enzyme complex, which is the site of photorespiratory CO2 and NH3 release. Although the proteins that constitute the complex are located within the mitochondria, because of their intimate association with photosynthesis their expression is controlled by light. Comparisons of the kinetics of mRNA accumulation between the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase and the H-protein of glycine decarboxylase during the greening of etiolated Arabidopsis thaliana suggest that their expression is controlled in parallel. A genomic clone for the H-protein (gdcH) was isolated from Arabidopsis and sequenced. The upstream region from -856 to +62 was fused to the beta-glucuronidase (GUS) reporter gene, and this construct was transformed into tobacco. This 5' upstream regulatory region appears to control GUS expression in a manner very similar to that of the endogenous H-protein gene. Constructs with deletions in the 5' upstream region were transformed into tobacco. These deletions revealed that light-dependent and tissue-specific expression was largely controlled by a 259-bp region between -376 and -117 bp. This region contains several putative GT boxes with the GGTTAA consensus core sequence. Once these strong light-dependent elements were removed, a second level of control was revealed. In constructs in which the gdcH 5' regulatory region was shortened to -117 bp or less, there was more GUS activity in the roots than in the leaves, and in dark-grown plants than in light-grown plants. This suggests that more proximal control elements may be responsible for the constitutive low levels of gene expression noted in all nonphotosynthetic tissues.
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PMID:Light-dependent and tissue-specific expression of the H-protein of the glycine decarboxylase complex. 748 Mar 20


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