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)

beta 2-Microglobulin (beta 2M) polymerizes to form amyloid fibrils that deposit and cause destructive bone lesions in patients on chronic dialytic therapy. beta 2 M is mitogenic to osteoblasts; however, its effect on bone mineralization is unknown. To determine whether beta 2M causes bone demineralization, neonatal mouse calvariae were incubated with and without beta 2M, and net calcium flux was calculated. Following a 48-h but not 3- or 24-h incubation, beta 2M (10(-8)-10(-6) M) induced a net calcium efflux. The efflux was similar to that observed with 10(-10) M parathyroid hormone (PTH) but less than that observed with 10(-8 M PTH. Devitalizing the calvariae resulted in a net calcium influx that was unaffected by the addition of beta 2M, indicating a cell-mediated phenomenon. The release of beta-glucuronidase, an osteoclast enzyme, increased after a 48-h but not a 24-h incubation with beta 2M. Calcitonin, an osteoclast inhibitor, blocked the beta 2M-induced calcium efflux and beta-glucuronidase release, suggesting osteoclast involvement. Thus beta 2M induces a dose- and time-dependent, cell-mediated calcium efflux from neonatal mouse calvariae that involves osteoclast stimulation.
Am J Physiol 1992 Sep
PMID:Beta 2-microglobulin induces calcium efflux from cultured neonatal mouse calvariae. 141 83

The antiprotozoal drug pentamidine [1,5-bis(4'-amidinophenoxy)pentane] has been previously shown to be metabolized by rat liver microsomes, and five of the seven putative primary metabolites have been identified. With the synthesis and identification of 5-(4'-amidinophenoxy)pentanoic acid and 5-(4'-amidinophenoxy)-1-pentanol as the remaining two metabolites, the primary metabolism of pentamidine in rats appears fully characterized. Use of [14C]pentamidine with rat liver microsomes confirms this conclusion, since no unidentified radioactive peaks were detected by high-performance liquid chromatography (HPLC). Isolated, perfused rat livers were used with [14C]pentamidine to identify secondary metabolites. Only two novel radioactive peaks were detected by HPLC analysis of perfused liver samples. The treatment of liver samples with sulfatase or beta-glucuronidase resulted in the reduction or elimination of these peaks and gave rise to peaks identified as para-hydroxybenzamidine and 5-(4'-amidinophenoxy)pentanoic acid. It was concluded from these results that only these two primary metabolites were conjugated with sulfate or glucuronic acid. After 4 h of incubation in the perfused liver system, approximately 15% of the recovered radiolabel was pentamidine. These results suggest that pentamidine metabolism can be rapid and extensive in rats.
Antimicrob Agents Chemother 1992 Sep
PMID:Primary and secondary metabolism of pentamidine by rats. 141 74

A high-performance liquid chromatographic method for the routine determination of elevated urinary levels of the serotonin metabolite 5-hydroxytryptophol (5-HTOL) is described. Urine samples were treated with beta-glucuronidase, and 5-HTOL was isolated by solid-phase extraction on a small Sephadex G-10 column prior to injection onto an isocratically eluted C18 reversed-phase column. Detection of 5-HTOL was performed electrochemically at +0.60 V vs. Ag/AgCl. The limit of detection was ca. 0.05 microM, and the intra-assay coefficients of variation were below 6% with urine samples containing 0.2 and 2.1 microM 5-HTOL and a standard solution of 2.0 microM (n = 5). The recovery of 5-HTOL after the sample clean-up procedure was close to 100%. A good correlation (r2 = 0.97; n = 12) was obtained between the present method and a sensitive and specific gas chromatographic-mass spectrometric method. The total (free plus conjugated) 5-HTOL levels in urine were normally below 0.2 microM, but after an acute dose of alcohol they increased to 0.5-15 microM.
J Chromatogr 1992 Sep 02
PMID:Determination of urinary 5-hydroxytryptophol by high-performance liquid chromatography with electrochemical detection. 142 82

We report on a 20-year-old male with a beta-glucuronidase (GUSB) deficiency mucopolysaccharidosis. He had pectus carinatum, gross thoracic kyphoscoliosis, and hip dysplasia, a picture which became conspicuous after age 4 years. Hepatosplenomegaly, herniae, corneal clouding, and neurological abnormalities were absent. Although he had Alder-type granulations in his polymorphonuclear leukocytes, the urine did not contain a significant excess of mucopolysaccharides. Electron microscopic examination of skin and gingival biopsies, leukocytes, and cultured skin fibroblasts showed numerous single membrane-limited vacuoles either empty or filled with fibrillogranular material; this last tissue did not contain metachromatic granules. Radiographs demonstrated a distinct spondyloepiphyseal dysplasia in which the most striking changes were confined to the thoracic spine (flattening and collapse in T7, T8 and T10 vertebral bodies) and to the femoral capital epiphyses (irregularities and fragmentation). The activity of GUSB in the patient's serum, leukocytes, and fibroblasts was severely decreased; the GUSB activity in the serum and leukocytes from the parents and 2 asymptomatic sibs was subnormal. Immunoblot analysis showed very low levels of cross-reactive material towards anti-GUSB antiserum in the patient's leukocyte and fibroblast extracts. This patient was more severely affected in his skeleton than other described patients with an oligosymptomatic chronic form. This case broadens the clinical and biochemical picture associated with GUSB deficiency and may represent a new variant of the disease.
Am J Med Genet 1992 Sep 15
PMID:Mucopolysaccharidosis type VII (beta-glucuronidase deficiency): a chronic variant with an oligosymptomatic severe skeletal dysplasia. 145 83

The NIa proteinase encoded by tobacco etch potyvirus catalyzes six processing events, three of which occur by an autoproteolytic mechanism. Autoproteolysis is necessary to cleave the boundaries of both NIa and the 6-kDa protein, which is located adjacent to the N terminus of NIa in the viral polyprotein. As a consequence, NIa may exist in a free form or in a transient polyprotein form containing the 6-kDa protein. While the majority of NIa molecules localize to the nuclei of infected cells, a fraction of the NIa pool is attached covalently to the 5' terminus of genomic RNA in the cytoplasm. To determine whether the presence of the 6-kDa protein affects the nuclear transport properties of NIa, we have generated transgenic plants that express genes encoding a reporter enzyme, beta-glucuronidase (GUS), fused to NIa or NIa-containing polyproteins. The NIa/GUS fusion protein was detected by histochemical analysis in the nucleus. Similarly, an NIa/GUS fusion protein that arose by autoproteolysis of a 6-kDa/NIa/GUS polyprotein was found in the nucleus. In contrast, fusion protein consisting of 6-kDa/NIa/GUS, which failed to undergo proteolysis because of the presence of a Cys-to-Ala substitution in the proteolytic domain of NIa, was detected in the cytoplasm. The inhibition of NIa-mediated nuclear transport was not due to the Cys-to-Ala substitution, since this alteration had no effect on translocation in the absence of the 6-kDa protein. These results indicate that the 6-kDa protein impedes nuclear localization of NIa and suggest that subcellular transport of NIa may be regulated by autoproteolysis.
J Virol 1992 Sep
PMID:Regulation of nuclear transport of a plant potyvirus protein by autoproteolysis. 150 Dec 98

Different factors involved in the early steps of the T-DNA transfer process were studied by using a beta-glucuronidase gene (gusA) as a reporter in Nicotiana glauca leaf disc transformation experiments. The levels of transient expression of the gusA gene in leaf discs infected with several strains or vir mutants correlated well with their virulence phenotype, except for virC mutants. The rate of T-DNA transfer was shown to be stimulated in the case of non-oncogenic strains by the co-transfer of small amounts of oncogenic genes. It was found that the location of the T-DNA in the Agrobacterium genome affected the T-DNA transfer rate especially in virC mutants. The virC mutants transferred the gusA-containing T-DNA located on a binary vector more efficiently than the oncogenic T-DNA of the Ti plasmid. Although wild-type strains induced high levels of gusA expression early after infection, the gusA expression appeared to be lost late after infection in the infected leaf discs. In contrast, in leaf discs infected by virC mutants the level of gusA expression increased steadily in time. A model explaining these results is presented.
Plant Mol Biol 1992 Sep
PMID:Factors affecting the rate of T-DNA transfer from Agrobacterium tumefaciens to Nicotiana glauca plant cells. 151 Nov 27

A functional analysis of the promoter from the wheat alpha-amylase gene alpha-Amy2/54 is described. Mutant alpha-Amy2/54 promoters containing replacements or deletions were constructed and their ability to direct expression of the reporter gene beta-glucuronidase (GUS) in gibberellin-responsive oat aleurone protoplasts analysed. Chimaeric promoters using regions of the cauliflower mosaic virus (CaMV) 35S and alpha-Amy2/54 promoters were also analysed. The results suggest that at least three regions within the alpha-Amy2/54 promoter contain cis elements that are necessary for high-level gibberellin-regulated transcription. Fusion of 1.8 kb of promoter sequence upstream from -117 bp to a minimal (-55 CaMV 35S) promoter gave rise to hormone-independent expression implying that the region 3' to -117 bp contains an element which represses transcription in the absence of gibberellin or presence of abscisic acid.
Plant Mol Biol 1992 Sep
PMID:Localisation of cis elements in the promoter of a wheat alpha-Amy2 gene. 151 Nov 36

Stable transformation of Norway spruce tissue has been obtained following bombardment of mature somatic embryos with pRT99gus, a plasmid that contains neo coding for NPTII, and gusA, coding for beta-glucuronidase, both fused to the CaMV 35S promoter. At least 8 lines have been stably transformed (over 15 months in culture) following bombardment and selection on kanamycin. Polymerase chain reaction analyses showed a high frequency of cotransformation of the gusA and neo genes. The frequency of coexpression of the selected and unselected markers was 100%. DNA/DNA hybridization of one transformed line provided conclusive evidence of stable integration and showed copy numbers of over 10 plasmid sequences per genome. None of the transformed lines has remained embryogenic.
Plant Mol Biol 1992 Sep
PMID:Genetic transformation of Norway spruce (Picea abies (L.) Karst) using somatic embryo explants by microprojectile bombardment. 151 Nov 38

The LAC4 gene encoding the beta-galactosidase (beta Gal) of the yeast, Kluyveromyces lactis, was cloned on a 7.2-kb fragment by complementation of a lacZ-deficient Escherichia coli strain. The nucleotide sequence of the structural gene, with 42 bp and 583 bp of the 5'- and 3'-flanking sequences, respectively, was determined. The deduced amino acid (aa) sequence of the K. lactis beta Gal predicts a 1025-aa polypeptide with a calculated M(r) of 117618 and reveals extended sequence homologies with all the published prokaryotic beta Gal sequences. This suggests that the eukaryotic beta Gal is closely related, evolutionarily and structurally, to the prokaryotic beta Gal's. In addition, sequence similarities were observed between the highly conserved N-terminal two-thirds of the beta Gal and the entire length of the beta-glucuronidase (beta Glu) polypeptides, which suggests that beta Glu is clearly related, structurally and evolutionarily, to the N-terminal two-thirds of the beta Gal. The structural analysis of the beta Gal alignment, performed by mean secondary structure prediction, revealed that most of the invariant residues are located in turn or loop structures. The location of the invariant residues is discussed with respect to their accessibility and their possible involvement in the catalytic process.
Gene 1992 Sep 01
PMID:Sequence of the Kluyveromyces lactis beta-galactosidase: comparison with prokaryotic enzymes and secondary structure analysis. 151 85

Primary aromatic amines have been identified epidemiologically as human carcinogens. It has been suggested that the target organ affected by aromatic amines is dependent on the rate of metabolic activation. Epidemiological studies have shown an association between low acetyl transferase activity and bladder cancer risk. On this basis, our working hypothesis was that the slow acetylators could follow in a higher extent the metabolic pathway independent of N-acetylation, leading to the excretion of conjugates of electrophyles with glucuronic acid. The instability of these glucuronides could be responsible for the association between arylamine-induced bladder cancer and slow acetylator phenotype. A total of 153 individuals were included in this study: 70 exposed to arylamines (working in textile industry) and 83 nonexposed. The following parameters were determined in urine: mutagenic index in the absence of metabolic activation, S9; mutagenic index in the presence of S9; and the mutagenic index after incubation of the urine with beta-glucuronidase. All individuals were phenotyped according to their capacity of N-acetylation by using isoniazid as drug test. The results show that the mutagenic index after incubation of the urine with beta-glucuronidase is statistically higher in exposed subjects when compared with nonexposed individuals (P less than 0.001), this parameter being statistically higher among exposed subjects who were slow acetylators than among rapid metabolizers, independent of the fact that they were smokers or nonsmokers. There were no significant differences between groups for the mutagenicity in urine not incubated with beta-glucuronidase.
Cancer Res 1992 Sep 15
PMID:Urinary mutagenicity and N-acetylation phenotype in textile industry workers exposed to arylamines. 151 45


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