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

Uridine 5'-diphosphoglucuronic acid-fortified hepatic microsomes from dogs, rats, or humans rapidly metabolized [3H]-N-hydroxy-2-naphthylamine (N-HO-2-NA) to a water-soluble product that yielded 98% of the parent N-hydroxy amine upon treatment with beta-glucuronidase. The metabolite was identified as N-(beta-1-glucosiduronyl)-N-hydroxy-2-naphthylamine from ultraviolet, infrared, and mass spectral analyses of the glucuronide and its nitrone derivative. Incubation of N-hydroxy-1-naphthylamine (N-HO-1-NA), N-hydroxy-4-aminobiphenyl (N-HO-ABP), or the N-hydroxy derivatives of 2-aminofluorene, 4-aminoazobenzene, or N-acetyl-2-aminofluorene with uridine 5'-diphosphoglucuronic acid-fortified hepatic microsomes also yielded water-soluble products. beta-Glucuronidase treatment released 80 to 90% of the [3H]-NHO-1-NA and [3H]-N-HO-ABP conjugates as tritiated ether-extractable derivatives. N-HO-1-NA, N-HO-2-NA, and N-HO-ABP and the glucuronides of these N-hydroxy arylamines were relatively stable and nonreactive near neutral pH. At pH 5, the N-glucuronide of N-HO-2-NA and the presumed N-glucuronides of N-HO-1-NA and N-HO-ABP were rapidly hydrolyzed to the N-hydroxy arylamines that were then converted to reactive derivatives capable of binding covalently to nucleic acids. These data support the concept that arylamine bladder carcinogens are N-oxidized and N-glucuronidated in the liver and that the N-glucuronides are transported to the urinary bladder. The hydrolysis of the glucuronides to N-hydroxy arylamines and the conversion of the latter derivatives to highly reactive electrophilic arylnitrenium ions in the normally acidic urine of dogs and humans may be critical reactions for tumor induction in the urinary bladder.
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PMID:Hepatic microsomal N-glucuronidation and nucleic acid binding of N-hydroxy arylamines in relation to urinary bladder carcinogenesis. 1 29

An androgen binding activity with characteristics similar to ABP is present in a particulate fraction (105,000 g pellet) obtained by differential centrifugation of seminiferous tubules, impure Sertoli cells and impure germ cells homogenates. Purification of germ cells through albumin gradients, results in almost a complete loss of androgen binding activity in the purified germ cell suspensions. Furthermore, Sertoli cell enriched testes from 22-, 32- and 40-day old rats showed increases in particulate androgen binding, when compared to matched controls, parallel to increments in the activity of a Sertoli cell marker enzyme (beta-glucuronidase). These results suggest that particulate androgen binding activity is only present in Sertoli cells and this protein may play a role in the compartmentalization of androgens in the testis.
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PMID:Relative cellular distribution of particulate androgen binding between Sertoli and germ cells in rat testis. 654 Dec 77

Urinary N-hydroxy metabolites of carcinogenic arylamines were investigated for their abilities to induce unscheduled DNA synthesis (UDS) in human urothelial cell lines HCV 29, HU 1734, and HU 1752, and in a primary culture of human urothelial cells. N-Hydroxy-2-aminofluorene (CAS: 53-94-1; N-OH-AF), N-hydroxy-2-acetylaminofluorene (CAS: 53-95-2; N-OH-AAF), and the N-glucuronide of N-OH-AF induced UDS in HCV 29, HU 1734, and HU 1752. N-Hydroxy-4-aminobiphenyl (CAS: 6810-26-0; N-OH-ABP), N-hydroxy-4-acetylaminobiphenyl (CAS: 4463-22-3; N-OH-AABP), N-hydroxy-2-aminonaphthalene (CAS: 613-47-8; N-OH-AN), N-hydroxy-2-acetylaminonaphthalene (CAS: 2508-23-8; N-OH-AAN), and the N-glucuronide of N-OH-ABP induced UDS in HCV 29. However, the N-glucuronide of N-OH-AN did not. The O-glucuronide of N-OH-AAF induced UDS in HCV 29 only when beta-glucuronidase was present. Paraoxon inhibited the induction of UDS in HCV 29 by N-OH-AAF and N-acetoxy-2-acetylaminofluorene (CAS: 6098-44-8), but not by N-OH-AF. When examined in a primary culture of human urothelial cells, N-OH-AF, N-OH-AAF, N-OH-ABP, and N-OH-AABP were active, but N-OH-AN, N-OH-AAN, 2-aminonaphthalene (CAS: 91-59-8), 2-aminofluorene (CAS: 153-78-6;), and 4-aminobiphenyl (CAS: 92-67-1) were not. These results demonstrate that human urothelial cells are able to activate both acetylated and non-acetylated N-hydroxy metabolites of carcinogenic arylamines, and they suggest that O-glucuronidation may be a detoxification mechanism for N-arylacethydroxamic acids.
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PMID:Induction of DNA repair synthesis in human urothelial cells by the N-hydroxy metabolites of carcinogenic arylamines. 658 61

Human urine is known to contain substances that strongly inhibit bacterial mutagenicity of aromatic and heterocyclic amines in vitro. The biological relevance of these anti-mutagens was examined by comparing levels of tobacco-related DNA adducts in exfoliated urothelial cells from smokers with the anti-mutagenic activity in corresponding 24-h urine samples. An inverse relationship was found between the inhibition of PhIP-mutagenicity by urine extracts in vitro and two DNA adduct measurements: the level of the putatively identified ABP-dG adduct and the total level of all tobacco-smoke-related carcinogen adducts including those probably derived from PhIP. These substances appear to be dietary phenolics and/or their metabolites because (i) the anti-mutagenic activity of urine extracts (n=18) was linearly related to their content in phenolics; (ii) the concentration ranges of these substances in urine extracts were similar to those of various plant phenols (e.g., quercetin, isorhamnetin) for which an inhibitory effect on the liver S9-mediated mutagenicity of PhIP was obtained; (iii) treatment of urines with beta-glucuronidase and arylsulfatase enhanced both anti-mutagenicity and the levels of phenolics in urinary extracts; (iv) urinary extracts inhibited non-competitively the liver S9-mediated mutagenicity of PhIP as did quercetin, used as a model phenolics. Onion, lettuce, apples and red wine are important sources of dietary flavonoids which are probably responsible for the anti-mutagenicity associated with foods and beverages. After HPLC fractionation of urinary extracts, the distribution profile of anti-mutagenic activity corresponded roughly to that of onion and wine extract combined. Overall, our study strongly suggests that smokers ingesting dietary phenolics, probably flavonoids, are partially protected against the harmful effects by tobacco carcinogens within their bladder mucosal cells.
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PMID:Antimutagenic dietary phenolics as antigenotoxic substances in urothelium of smokers. 967 88