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)

1. Subcellular fractions of human placenta were prepared by nitrogen-bomb homogenization and differential centrifugation. 2. beta-Glucuronidase from placental lysosomes was purified 2100-fold on a protein basis. 3. The lysosomal enzyme, at different stages of purification, was characterized by using 4-methylumbelliferyl beta-d-glucuronide and phenolphthalein beta-d-glucuronide as substrates. 4. Only one isoenzyme of beta-glucuronidase was found in placenta; the enzyme in the endoplasmic reticulum appeared to be the same as the lysosomal enzyme. 5. The isoenzyme contained in normal plasma was different from that of the placenta. 6. The elevated beta-glucuronidase activity found in plasma obtained during pregnancy was due to increased activity of the normal plasma isoenzyme; no contribution was made by placental isoenzyme. 7. Plasma contained a heat-stable, non-diffusible activator of placental beta-glucuronidase. 8. A heat-stable competitive inhibitor of placental and plasma beta-glucuronidase was also present in plasma.
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PMID:Purification and characterization of lysosomal -glucuronidase from human placenta. 508 46

1. Acid phosphatase, cathepsin and beta-glucuronidase are released from rat-liver lysosomes by irradiation in vitro. Enzyme release is detectable after a dose of 1krad and increases with dose up to 100krads. 2. Maximum radiation effects were observed when the lysosomes were kept for 20hr. at 4 degrees or 20 degrees after irradiation. 3. An atmosphere of nitrogen considerably decreases enzyme release from lysosomes. 4. Enzyme release is enhanced by ascorbic acid and decreased by vitamin E. 5. Irradiation causes formation of lipid peroxides in lysosomes, and enzyme release increases with lipid peroxide formation. 6. It is suggested that lipid peroxide formation leads to rupture of the lysosome membrane and allows release of the contained hydrolytic enzymes.
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PMID:Release of enzymes from lysosomes by irradiation and the relation of lipid peroxide formation to enzyme release. 596 62

In order to resolve discrepancies in the literature concerning the subcellular localization of NADPH oxidase, we disrupted human neutrophils by nitrogen cavitation and fractionated the subcellular organelles on a discontinuous sucrose density gradient. The lightest fraction was 20- to 40-fold enriched for plasma membranes as determined by the marker enzymes alkaline phosphatase and phosphodiesterase I as well as by the ratio of lipid phosphorus to protein. There was a significant decrease in the specific activities of the granule markers myeloperoxidase, lysozyme, and beta-glucuronidase. An intermediate fraction was enriched in membrane markers but not to the extent the lightest fraction was enriched. This fraction contained more granular contamination, as shown by the marker enzymes. In contrast, the densest bands of the gradient were enriched for granule markers with little contamination by plasma membrane. Superoxide generation and NADP formation were primarily associated with the two membrane-enriched fractions from polymorphonuclear leukocytes stimulated with phorbol myristate acetate. The NADP formation associated with a dense granule fraction observed previously in our laboratory was probably due to a cyanide-stimulated oxidation of NADPH by myeloperoxidase.
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PMID:Co-localization of superoxide generation and NADP formation in plasma membrane fractions from human neutrophils. 609 76

Excretion of 3-(p-chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid (I) and its metabolites was studied in rats, beagle dogs, and rhesus monkeys given 20-mg/kg doses of 14C-labeled drug. The urine of rhesus monkeys contained two metabolites in addition to unchanged drug. Both metabolites were hydrolyzed to I by beta-glucuronidase and the hydrolysis was inhibited by 1,4-saccharolactone, indicating that they were glucuronides of I. One of the metabolites (III) was not hydrolyzed by dilute alkali. Its NMR spectrum indicated that the site of conjugation was one of the nitrogen atoms, i.e., it was a quaternary N-glucuronide. The FAB mass spectrum was in conformity with this assignment. This metabolite was not present in the urine of dogs or rats given labeled drug. The other metabolite (II) was excreted in the urine of all three species as well as in the bile of the rat. It was readily hydrolyzed by dilute alkali (pH 11 for 0.5 hr at 37 degrees C), indicating that this metabolite was an acyl glucuronide. The metabolite was stable at pH 4.5 but it was readily converted to three isomers at 37 degrees C within 1 hr at pH 6.5 and above. The mass spectra of the derivatized isomers and metabolite were similar. The isomers were hydrolyzed to I by dilute alkali but not by beta-glucuronidase. They exhibited reducing properties (whereas metabolite II did not), suggesting that they were formed by acyl migration of the aglycone to the second, third, and fourth carbon atoms of the glucuronic acid moiety. Acyl migration probably plays a role in the disposition of I as well as other drugs that form labile glucuronides.
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PMID:Metabolic formation of N- and O-glucuronides of 3-(p-chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid. Rearrangement of the 1-o-acyl glucuronide. 613 Sep 7

A human neutrophil protease, initially termed neutral peptide-generating protease, has been shown to cleave angiotensin II directly from angiotensinogen and has been identified as leukocyte cathepsin G. When purified neutrophils were disrupted by nitrogen cavitation and fractionated by differential centrifugation, 44 and 24% of the angiotensin II-generating activity was in the lysosomal and undisrupted cell fractions, respectively. Cytochalasin B-treated human neutrophils stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine released beta-glucuronidase, lysozyme, and angiotensin II-generating protease in a dose-dependent fashion, consistent with localization of this protease to the neutrophil granule. Individually purified angiotensin II-generating protease and cathepsin G had similar proteolytic and esterolytic activity for angiotensinogen and N-benzoyl-L-tyrosine ethyl ester on a weight basis, exhibited identical mobilities by SDS-gradient polyacrylamide gel electrophoresis and pH 4.3 disc-gel electrophoresis, and gave precipitin lines of antigenic identity on Ouchterlony analysis with goat antibody to the angiotensin II-generating protease. Thus, the angiotensin II-generating protease of human neutrophils has been identified as cathepsin G on the basis of subcellular localization, substrate specificity, physicochemical characteristics, and antigenic identity.
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PMID:Identification of a human neutrophil angiotension II-generating protease as cathepsin G. 617 48

The distribution, retention, and fate of 2[3H]aminoanthracene (2-AA) were determined in male Fischer-344 rats after inhalation exposure (70 micrograms/liter; activity mass median diameter = 2.1 micron) for 30 min. Radioactivity was found in the turbinates, trachea, lungs, liver, kidneys, and gastrointestinal tract 20 min after exposure. Lower quantities of radioactivity were found in fat, brain, testes, and muscle. Inhaled 2-AA was excreted predominantly in feces (80%). The remaining 2-AA was excreted in urine. Organic soluble radioactivity was released from urinary conjugates after treatment of urine with acid and with beta-glucuronidase. This result suggests that glucuronides of both ring- and N-hydroxy-2-AA were excreted. The remaining radioactivity was water soluble and accounted for approximately one-half of the total urinary radioactivity. The organic soluble radioactivity found after hydrolysis indicated that inhaled 2-AA is extensively metabolized by rats after inhalation and excreted as conjugated metabolites. Eighty-three percent of orally administered material was absorbed into the body from the GI tract; thus, material cleared by mucociliary action after inhalation would contribute to total body burden. 2-AA, a nitrogen substituted polycyclic aromatic hydrocarbon (PAH), was very similar to other PAHs in its rapid distribution throughout the body and in its route of excretion after inhalation.
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PMID:Distribution, retention, and fate of 2-aminoanthracene in rats after inhalation. 646 22

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

A nephropathy with severe tubular atrophy was observed in Beagle dogs after oral administration of K2HPO4 for 14 or 38 weeks. We describe the complete lysosomal degradation of atrophying tubular epithelial cells. During two experiments of 14 and 38 weeks duration, respectively, a total of 15 Beagle dogs received 0.8 g K2HPO4/kg body weight daily with their food. All dogs were examined clinically at regular intervals. Renal biopsies were taken in the fourth week from beagles of the 14-week study. Results were compared with those of control dogs. At the end of the experiments the animals were killed and necropsies done. Different stains and histochemical reactions were applied to paraffin sections of the kidneys. Acid phosphatase and beta-glucuronidase were found on cryostat sections. Kidneys fixed by perfusion of five Beagles from the 38-week study and three Beagles of the 14-week study, and from five control dogs, were examined electron microscopically. Ultrahistochemically, acid phosphatase was demonstrated. Clinically, the dogs in both experiments vomited, were cachectic, and had elevated creatinine and blood urea nitrogen. Morphologically, qualitatively identical changes were seen, but the renal damage was most marked at 38 weeks. There were disseminated tubular atrophy (usually of the proximal tubules), focal scar tissue and nephrocalcinosis. The following pathogenesis was established for the lesions of the proximal tubule: Tubular atrophy begins with loss of differentiation of epithelial cells. Enzyme histochemistry, ultrahistochemistry and electron microscopy show an increase in autophagic vacuoles and autophagolysosomes. The lysosomal bodies showing fusion enclose large parts of the cytoplasm as the process continues. Complete lysosomal degradation of epithelial cells and extrusion of large lysosomes into the tubular lumen follow. After complete enzymatic digestion of the intratubular detritus, the residue is empty, convoluted and collapsed tubular basement membrane. Atrophic tubular epithelial cells have many organelle-free zones at their base, which contain fine filamentous material resembling that of the basement membrane. The degradation process described here may explain why clinically the urinary sediment contains few cylinders and epithelial cells and why proteinuria decreases significantly toward the end of the experiment. So far, it is not clear whether the tubular basement membrane is synthesized by the tubular cells, by fibroblasts or by both cell types. The presence of basement membrane-like material in tubular epithelial cells and in parietal epithelial cells of the glomerulus favors the view that epithelial cells produce the basement membranes and that increased production of basement membrane-like material is a sign of loss of differentiation.
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PMID:[Potassium hydrogen phosphate induced nephropathy in the dog. I. Pathogenesis of tubular atrophy (author's transl)]. 742 30

In the paper presented here the following parameters on the skin of pure-bred Wistar inbred rats were investigated during the early postnatal maturation period: DNA-content (according to Burton 1956), nitrogen-content (according to Strauch 1965), beta-glucuronidase activity (according to Fishman 1974), partly also protein-content (according to Lowry 1951). At the same time, we tested if a single i.p. injection of 6-methyl-prednisolone, applied exactly at the same time of the day 24 h preceding the killing, has an influence on the above mentioned quantities in comparison to the control group (possibly dosage-dependent). In the observation period (2nd, 4th, 6th, 9th, and 14th day) a linear, statistically significant increase of the nitrogen-content could be stated on the skin. After an initial increase up to the 4th day of life the DNA-content significantly decreases during the following postnatal maturation period until the 14th day. These results could be obtained both in the control groups, and in the animals treated with different dosages of 6-methyl-prednisolone. It is of importance that these parameters (especially the cell and the DNA-content respectively) were not statistically significantly changed by pretreatment with the glucocorticoid at any day investigated. The total activity of the further tested lysosomal indicator-enzyme beta-glucuronidase increases during the postnatal maturation period up to its maximum on the 9th day of life before it decreases till the 14th day. The applied dosages of the glucucorticoid led to a general increase of the enzyme activity, which, however, was only exceptionally statistically significant. This enzyme induction could also by discussed in terms of a maturation acceleration. Dosage-dependent differences could partly be demonstrated.
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PMID:[The influence of a single glucocorticoid administration on the DNA and the nitrogen-content as well as on the beta-glucuronidase activity of rat skin during postnatal development (author's transl)]. 745 7


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