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)

Experimental lathyrism was produced in young albino mice with a diet containing 50% sweet pea seed (Lathyrus odoratus). After 7 days on the lathyritic diet, sections of themandibular molar and incisor periodontal ligaments, when oxidized and treated with aldehyde fuchsin, demonstrated enhanced staining of the oxytalan fibers and numerous vessels. At this time aldehyde fuchsin or orcein also revealed marked pathological changes in the periodntal ligament of all molars. When athyrism was prolonged for 12 weeks, both the molar and incisor oxytalan systems were still readily identifiable although the molar periodontal ligament continued to be serverely affected by lathyrism. The oxytalan fibers retained their characteristic tooth-vascular association in all of the lathyritic mice. Oxytalan fibers of the lathyritic and control animals showed similar reactions to enzyme digestion with beta-glucuronidase, elastase, and pepsin. However, gingival elastic fibers reacted in a different way from oxytalan fibers with beta-glucuronidase and elastase treatment. These findings indicate that in the lathyritic mouse the oxytalan fiber system of functioning teeth possesses a high degree of permanence and is metabolically distinct from collagen and elastic fibers.
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PMID:The oxytalan fiber system in the mandibular periodontal ligament of the lathyritic mouse. 6 1

A continuous cell line was previously obtained by Simian Virus (SV) 40 transformation of primary cultures of dissociated mouse fetal hypothalami. One clone from this cell line has been previously shown to possess some of the ultrastructural features, immunological properties and synthesizing capacities of magnocellular hypothalamic neurons which secrete vasopressin and neurophysins. The present paper reports on the morphological characterization of 14 other clones or subclones of the original cell line, using the following criteria: phase contrast microscopy, electron microscopy, Gomori's aldehyde fuchsin staining, cytochemical detection of beta-glucuronidase, immunochemical staining with antisera against bovine neurophysin I, bovine neurophysin II, lys-vasopressin, oxytocin, LH-RH and TRH. The results allowed the conclusion that the clones as well as the subclones can be distributed into two groups: 1) neurosecretory neurons which all possess several of the ultrastructural and cytochemical features of the neurophysin-vasopressin synthesizing clone, and 2) primitive nerve cells which are devoid of such features but display numerous bundles of filaments. In addition some clones were found to display intermediate features between groups 1 and 2. A similar diversity was observed within clones of the original strain and subclones of a neurosecretory clone. It is suggested that the primitive clones could represent precursors of the neurosecretory clones.
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PMID:Ultrastructural and cytochemical features of SV 40 transformed hypothalamic cell lines. 18 90

The biological transformation of phenyramidol (I), some of which is also excreted unchanged, occurs by three main degradative pathways: 1. Hydroxylation of the pyridine ring in position 3 (metabolite V) and 5 (metabolite VI). 2. Cleavage of the ethanolamine chain with the formation of 2-aminopyridine (metabolite II) and presumably mandelic aldehyde. 3. Conjugation with glucuronic acid (metabolite III). Secondary reactions result in the production of: benzoyl carbinol (metabolite XV), benzoic acid (metabolite XI), mandelic acid (metabolite XII) and the glucuronides of V, VI, VII, XII and possibly II (metabolites VIII, IX, X, XIII and IV), all of which were also found as free, unconjugated compounds. A further, unusual reaction is the dimerisation of metabolite VI with the formation of a dipyridyl derivative (metabolite VII), which is excreted partly as the free compound, but mainly as the glucuronide (metabolite X). The occurrence of 2-(N-benzylamino)-pyridine (XIV) in the urine could not be explained. Four futher excretory products (metabolites XVI, XVII, XVIII and XIX) were not identified; XVI and XVII were extracted at an alkaline pH, whereas XVIII and XIX were extracted under neutral conditions. They could be detected both as free compounds, and after hydrolysis with HCl or alkali, but not after treatment with beta-glucuronidase.
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PMID:[Isolation and identification of some metabolites of phenyramidol (Cabral) from human urine (author's transl)]. 92 36

1. The metabolism of vanillin, isovanillin and the corresponding alcohols and acids in rats was investigated using t.l.c., g.l.c. and combined g.l.c.-mass spectrometry. 2. Oral dosage (100 mg/kg) of the aldehyde resulted in urinary excretion of most metabolites within 24 h, mainly as glucuronide and/or sulphate conjugates although the acids formed were also excreted free and as their glycine conjugates. In 48 h 94% of the dose of vanillin was accounted for as follows (%) : vanillin (7), vanillyl alcohol (19), vanillic acid (47), vanilloylglycine (10), catechol (8), 4-methylcatechol (2), guaiacol (0-5) and 4-methylguaiacol (0-6). Similarly, 89% of the dose of isovanillin was accounted for as follows: isovanillin (19), isovanillyl alcohol (10), isovanillic acid (22), vanillic acid (11), isovanilloylglycine (19), catechol(7) and 4-methylcatechol (1). Protocatechuic acid was also formed from both aldehydes. 3. By means of (a) investigation of biliary metabolites, (b) prevention of biliary excretion, (c) suppression of intestinal bacteria with neomycin sulphate and (d) inhibition of intestinal beta-glucuronidase with saccharo-1,4-lactone, it was found that glucuronides of the aldehydes and their respective alcohol and acid derivatives are excreted in the bile and that the conjugates are metabolized by the intestinal bacteria to toluene derivatives and decarboxylated products.
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PMID:The metabolism of vanillin and isovanillin in the rat. 115 98

Granule laden astrocytes exhibiting an affinity for chrome alum hematoxylin and aldehyde fuchsin (Gomori stains) have been described in the periventricular brain of all terrestrial vertebrate species examined to date including humans. The astrocytic inclusions are rich in sulfhydryl groups, emit an orange-red autofluorescence, and stain intensely with diaminobenzidine, a marker of endogenous peroxidase activity. The distinct autofluorescence pattern and the absence of neutral lipid, acid phosphatase, and beta-glucuronidase activity exclude lipofuscin or lysosomes as components of these astrocytic granules. The emission of orange-red autofluorescence and the nonenzymatic nature of the peroxidase activity implicate the presence of porphyrins and metalloporphyrins such as heme as major constituents of these cytoplasmic gliosomes. The role of Gomori-positive astrocytes under normal and pathologic conditions is incompletely understood. In vivo, numbers of astrocytic granules increase as a function of advancing age, in response to chronic estrogen stimulation, and following X-irradiation. In vitro, these cells accumulate with increasing time in culture and following exposure to the sulfhydryl agent, cysteamine. Gomori-positive astrocytes may supply heme to neurons for the synthesis of cytochromes, catalases, and other heme enzymes. They may play a role in photostimulation of sexual cyclicity, the promotion of neuritic development, the degradation of toxic lipoperoxides, and the metabolism of various neurotransmitters. Conversely, these cells may contribute to the pathogenesis of several neurologic and neuroendocrine disorders. Examples of the latter include a) augmentation of goldthioglucose neurotoxicity, b) induction of hypothalamic anovulation and reproductive failure, c) exacerbation of porphyric encephalopathy, and d) potentiation of parkinsonism and other free radical-related neurodegenerations.
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PMID:Gomori-positive astrocytes: biological properties and implications for neurologic and neuroendocrine disorders. 171 59

The metabolism of tocainide, an oral antiarrhythmic agent, was studied in male Wistar rats following oral administration of 15 mg/kg of tocainide hydrochloride. Qualitative and quantitative identification of the metabolites in urine was carried out by GC-mass spectrometry and electron capture detector gas chromatography. About 15-20% of the dose administered was excreted as intact drug in the urine. An additional 20% of the dose was present as acid hydrolysable conjugates. Enzymatic hydrolysis (beta-glucuronidase) revealed half of the acid hydrolysable conjugates to be a glucuronide. The enzyme mediated hydrolysis was blocked by its specific inhibitor saccharo-1,4-lactone. N-acetyl tocainide, an oxidatively deaminated tocainide, an aldehyde adduct of tocainide, and a cyclic hydantoin derivative of tocainide were also identified as metabolites in the urine samples.
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PMID:Metabolism of tocainide in the rat. 680 12

A copper amine oxidase encoding gene, atao1, has been isolated and characterized from Arabidopsis thaliana. Sequence analysis reveals that atao1 encodes a 668 amino acid polypeptide (ATAO1) with 48% identity to copper amine oxidases from pea and lentil. The promoter region of atao1 was transcriptionally fused with the reporter genes encoding beta-glucuronidase and modified green fluorescent protein. Analysis of transgenic Arabidopsis together with in situ hybridization of wild-type plants reveals temporally and spatially discrete patterns of gene expression in lateral root cap cells, vascular tissue of roots, developing leaves, the hypocotyl, and in the style/stigmatal tissue. Enzyme activity assays show that ATAO1 preferentially oxidizes the aliphatic diamine putrescine with production of the corresponding aldehyde, ammonia and hydrogen peroxide, a recognized plant signal molecule and substrate for peroxidases. Histochemical analysis reveals that atao1 expression in developing tracheary elements precedes and overlaps with lignification and therefore is a good marker for vascular development. In both vascular tissue and the root cap, atao1 expression occurs in cells destined to undergo programmed cell death.
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PMID:Developmental expression and biochemical analysis of the Arabidopsis atao1 gene encoding an H2O2-generating diamine oxidase. 968 Oct 17

The process of degranulation of mast cells and neutrophils contributes to inflammatory disorders. Activation of microglial cells and macrophages is believed to be involved in inflammatory, infectious and degenerative diseases of the CNS. Combining the potent inhibition of chemical mediators released by the degranulation of mast cells or neutrophils and from the activated microglial cells or macrophages, would lead to a promising anti-inflammatory agent for the treatment of peripheral and central inflammation. A series of chalcone derivatives have been reported to have potent anti-inflammatory activity. In an effort to continually develop potent anti-inflammatory agents, novel series of chalcones, 2'-hydroxy- and 2',5'-dihydroxychalcones were synthesized and their inhibitory effects on the activation of mast cells, neutrophils, microglial cells and macrophages were evaluated in-vitro. The chalcones were prepared by Claisen-Schmidt condensation of appropriate acetophenones with an appropriate aromatic aldehyde. The alkoxychalcones were prepared with appropriate hydroxychalcones and alkyl iodide and the dihydroxychalcones were prepared by hydrogenation of an appropriate chalcone with Pd/C. Almost all of the hydroxychalcones exhibited potent inhibitory effects on the release of beta-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB). Of the hydroxychalcones, compound 1 was the most potent inhibitor of the release of beta-glucuronidase (IC50=1.6+/-0.2 microM) and lysozyme (IC50=1.4+/-0.2 microM) from rat neutrophils stimulated with fMLP/CB. Almost all of the 2',5'-dialkoxychalcones exhibited potent inhibitory effects on nitric oxide (NO) formation from murine microglial cell lines N9 stimulated with lipopolysaccharide (LPS). Of these, compound 11 showed the greatest effect (IC50=0.7+/-0.06 microM). The present results demonstrated that most of the chalcone derivatives have an anti-inflammatory effect. The inhibitory effects of dialkoxychalcones, 10-12 on inflammation are probably not due to the inhibition of mast cells and neutrophil degranulation, but are mediated through the suppression of NO formation from N9 cells.
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PMID:Synthesis and anti-inflammatory effect of chalcones. 1071 46

The metabolic pattern of the imidazole fungicide prochloraz [N-propyl-N-[2-(2,4,6-trichlorophenoxy)ethyl]imidazole-1-carboximide] was investigated in rainbow trout (Oncorhynchus mykiss). Following a single oral administration of [(14)C]prochloraz, levels 4.3 +/- 4.1 and 3.9 +/- 1.8% of the dose were excreted in the bile after 48 h in male and female animals, respectively. Urinary radioactivity accounted for 1.3 +/- 0.4 and 2.4 +/- 1.1% of the dose over the same period in males and females. Metabolites from both matrices were separated by reversed-phase HPLC with radioactive detection and analyzed by positive and/or negative electrospray ionization mass spectrometry. No unchanged prochloraz was detected in the analyzed excreta. The major biotransformation products in bile were the aldehyde corresponding to the cleavage of the imidazole ring, N-2-(2,4,6-trichlorophenoxy)ethylurea, and the glucuronide conjugate of 2,4,6-trichlorophenoxyethanol. In urine, the major metabolite was 2,4,6-trichlorophenoxyacetic acid. On the basis of enzymatic hydrolysis by beta-glucuronidase and LC-MS analyses, this study demonstrates that rainbow trout are able to biotransform prochloraz, mainly as glucuronide conjugates.
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PMID:Identification of the major metabolites of prochloraz in rainbow trout by liquid chromatography and tandem mass spectrometry. 1151 73

The in vitro and in vivo disposition of DPC 423 was investigated in mice, rats, dogs and humans and the metabolites characterized by LC/MS, LC/NMR and high field-NMR. The rodents produced several metabolites that included an aldehyde (M1), a carboxylic acid (M2), a benzyl alcohol (M3), glutamate conjugates (M4 and M5), an acyl glucuronide (M6) and its isomers; a carbamyl glucuronide (M7); a phenol (M8) and its glucuronide conjugate (M9), two glutathione adducts (M10 and M11), a sulfamate conjugate (M12), isomers of an oxime metabolite (M13), and an amide (M14). Humans and dogs produced less complex metabolite profiles than rats. While unchanged DPC 423 was the major component in plasma and urine samples, differences in the metabolic disposition of this compound among species were noted. M1 is believed to be rapidly oxidized to the carboxylic acid (M2), which forms the potentially reactive acyl glucuronide (M6). The formation of novel glutamate conjugates (M4 and M5) and their role in depleting endogenous glutathione have been described previously. The carbamyl glucuronide M7, found as the major metabolite in rats and in other species, was considered nonreactive and was easily hydrolyzed to the parent compound in the presence of beta-glucuronidase. The identification of GSH adducts M10 and M11 led us to postulate the existence of at least two reactive intermediates responsible for their formation, an epoxide and possibly a nitrile oxide, respectively. Although the formation of GSH adducts such as M10 from epoxides has been described before, there are no reports to date describing the existence of a GSH adduct (M11) of an oxime. The formation of a sulfamate conjugate (M12) formed by direct coupling of sulfate to the nitrogen of benzylamine is described. A mechanism is proposed for the formation of the oxime (M13) that involves sequential oxidation of the benzylamine to the corresponding hydroxylamine and nitroso intermediate. The rearrangement of the nitroso intermediate is believed to produce the oxime (M13). In vitro studies suggested that both the oxime (M13) and the aldehyde (M1) were precursors to the carboxylic acid (M2). This is the first demonstration of carboxylic acid formation via an oxime intermediate produced from an amine. The stability of DPC423 in plasma obtained from several species was studied. Significant species differences in the plasma stability of DPC 423 were observed. The formation of the aldehyde metabolite (M1) was found to be catalyzed by a semicarbazide-sensitive monoamine oxidase (SSAO) found in plasma of rabbits, dogs, and rhesus monkeys. Rat, chimpanzee, and human plasma did not form M1.
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PMID:Disposition of 1-[3-(aminomethyl)phenyl]-N-[3-fluoro-2'- (methylsulfonyl)-[1,1'-biphenyl]-4-yl]-3-(trifluoromethyl)- 1H-pyrazole-5-carboxamide (DPC 423) by novel metabolic pathways. Characterization of unusual metabolites by liquid chromatography/mass spectrometry and NMR. 1180 May 97


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