Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Different cellular fractions of guinea-pig placenta were incubated in the presence of (7n-3H) testosterone. Microsomal aromatization of 3H-testosterone into estrone and estradiol-17beta was demonstrated in the presence of NADPH. The predominance of estrone after incubation with 17beta-hydroxylated precursors, (7n-3H) testosterone and (6,7-3H) estradiol-17beta, indicate that there is a microsomal 17beta-hydroxysteroid dehydrogenase activity. In this report, cytosolic sulfurylation of estrogens is demonstrated. This latter activity represents a quite original characteristic of the placental metabolism of estrogens in guinea-pigs. In contrast with the human placenta where there is considerable sulfatase activity, the guinea-pig placenta can sulfurylate estrogens.
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PMID:Conversion, in vitro, of (7n-3H) testosterone to estrone and estradiol-17beta and their 3-sulfate conjugate by the guinea-pig placenta. 71 21

Dihydrodiol dehydrogenase (DD; EC 1.3.1.20) purified to homogeneity from rat liver cytosol will catalyze the NAD(P)(+)-dependent oxidation of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (B[a]P-diol) to yield benzo[a]pyrene-7,8-dione (BPQ). To verify that BPQ is a metabolite of B[a]P-diol in rat liver, an S100 fraction was supplemented with NAD+ and NADP+, and the formation of BPQ was followed by reverse-phase HPLC. The identity of BPQ was established by co-chromatography with an authentic standard (under different solvent conditions) and by RP-HPLC using a diode-array detector which established that the metabolite shared spectral identity with BPQ. The formation of BPQ in the S100 fraction was blocked by either a competitive inhibitor (indomethacin) or a suicide substrate [1-(4-nitrophenyl)-propen-1-ol] for DD, indicating that BPQ was being formed by this enzyme. To assess the contribution of DD to the metabolism of [3H]B[a]P-diol, subcellular fractions obtained from uninduced rat liver were fortified with co-factors to optimize the activity of enzymes that would compete for this proximate carcinogen. Under these conditions, S100 fractions fortified with NAD+ and NADP+ metabolized 25% of the B[a]P-diol, producing 731 +/- 154 pmol of BPQ. In contrast, rat liver microsomes fortified with an NADPH generating system metabolize 75% of the B[a]P-diol producing 2614 +/- 379 pmoles of benzo[a]pyrene-tetrahydrotetrols. Rat liver homogenates (S10) fortified with either uridine diphosphoglucuronic acid or phosphoadenosine phosphosulfate produced 180 +/- 56 and 95 +/- 31 pmoles of conjugates respectively, which were recovered as B[a]P-diol after treatment of the aqueous phase with either beta-glucuronidase or aryl sulfatase. Of the metabolites analyzed BPQ was formed in the second largest amount. These studies show that in uninduced rat liver DD may play a significant role in the metabolism of B[a]P-diol. The metabolic fate of BPQ remains to be determined.
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PMID:Contribution of dihydrodiol dehydrogenase to the metabolism of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene in fortified rat liver subcellular fractions. 139 42

Comparison of the mutagenicity of nine isomeric benzo(a)pyrenyl [B(a)P] phenols conjugated with either sulfate or glucuronide was carried out using strain Salmonella typhimurium TA98. Of the nine conjugates tested, only B(a)P-1-sulfate was mutagenic. Accordingly, the mutagenicity of B(a)P-1-sulfate was compared with that of B(a)P and 1-hydroxybenzo(a)pyrene [B(a)P-1-OH] in the presence and absence of rat lung S9 and Aroclor-induced liver S9 with and without an NADPH-generating system. B(a)P-1-sulfate was slightly mutagenic, whereas B(a)P and the 1-hydroxy derivative were nonmutagenic when S9 fractions and NADPH were omitted. Addition of induced liver S9 with NADPH caused mutagenicity with B(a) -1-OH greater than B(a)P greater than B(a)P-1-sulfate. B(a)P-1-sulfate was the only mutagenic species when lung S9 was added. This mutagenicity did not require NADPH. Sodium sulfite, an inhibitor of arylsulfatase, decreased the mutagenicity of B(a)P-1-sulfate. These data suggest that a unique mutagenic species is generated from B(a)P-1-sulfate via arylsulfatase in rat lung.
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PMID:Mutagenicity of benzo(a)pyrenyl-1-sulfate in the Ames test. 157 48

After ip administration of 3-tert-butyl-4-hydroxyanisole (3-BHA) to rats, two previously undocumented metabolites 2-tert-butyl-5-methylthiohydroquinone (TBHQ-5-SMe) and 2-tert-butyl-6-methylthiohydroquinone (TBHQ-6-SMe) were identified in the urine by comparison with the authentic samples by GC/MS. In addition to these metabolites, 3-tert-butyl-4,5-dihydroxyanisole was also detected in the urine hydrolyzed by beta-glucuronidase/sulfatase. Administration of tert-butylhydroquinone (TBHQ), an O-demethylated metabolite of 3-BHA, also resulted in the formation of the S-containing metabolites, TBHQ-5-SMe and TBHQ-6-SMe. After incubation of TBHQ with rat liver microsomes in the presence of glutathione (GSH), two metabolites were isolated and purified by HPLC. The metabolites were identified as 2-tert-butyl-5-(glutathion-S-yl)hydroquinone and 2-tert-butyl-6-(glutathion-S-yl)hydroquinone by 1H- and 13C-NMR spectrometry and by fast atom bombardment-mass spectrometry. The formation of TBHQ-GSH conjugates required NADPH, molecular oxygen, and GSH. Cytochrome P-450 inhibitors such as SKF 525-A and metyrapone markedly inhibited the formation of TBHQ-GSH conjugates in vitro. These results suggest that TBHQ is converted by cytochrome P-450-mediated monooxygenases to a reactive metabolite, 2-tert-butyl-p-benzoquinone (TBQ), which then conjugates with GSH to form TBHQ-GSH conjugates. GSH S-transferase activities do not seem to play a role in GSH conjugation reaction to TBQ because cytosol fraction from rat liver homogenates did not enhance the microsome-mediated production of TBHQ-GSH conjugates.
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PMID:Identification and structure characterization of S-containing metabolites of 3-tert-butyl-4-hydroxyanisole in rat urine and liver microsomes. 168 7

Kinetic studies of the histochemical and histoenzymatic behavior of rabbit pancreatic parenchymas were performed 5, 30 and 90 days after Wirsung duct ligation. In control pancreas, some enzyme activities (EA) were more prominent in Langerhans islets [glucose-6-phosphatase, glucose-6-phosphate dehydrogenase (DH), isocitrate DH, glycerol-3-phosphate DH, NADPH DH], others were strongly marked in acini and ducts (alkaline phosphatase, beta-glucuronidase, acid esterase aryl-sulfatase). Histochemical and enzyme abnormalities observed in experimental rabbits reflect the post-ligation degenerative and reactive processes in both exocrine and endocrine pancreas: (1) the decrease in Krebs cycle and pentose pathway linked EA and the increased lysosomal and acid phosphatase EA reflect early (day 5) degeneration and necrosis of islets and acini (day 30); (2) proliferative processes in developed ductal epithelia are shown by an increase in both glycolytic and lysosomal EA (days 30 and 90); (3) connective tissue neogenesis and interstitial fibrosis occurred as shown by activated beta-glucuronidase, aryl-sulfatase, alkaline phosphatase and increased ribonucleoproteins and glycoaminoglycans contents (day 30); (4) on day 90, the neoformed cell clusters presenting glucose-6-phosphatase positivity (B-cell marker) are seen in the pancreas remnant. At the same time, blood insulin level increases correlated with a decrease of hyperglycemia.
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PMID:Cell features in pancreas of prediabetic and diabetic rabbits after Wirsung duct ligation. Histochemical and histoenzymatic studies. 233 24

Previous results have suggested that key intermediates in the activation of 2-nitrotoluene and 2,6-dinitrotoluene are 2-aminobenzyl alcohol and 2-amino-6-nitrobenzyl alcohol, respectively. In order to determine the metabolic pathway(s) involved in the activation steps, calf thymus DNA and [14C]-2-aminobenzyl alcohol or [14C]-2-amino-6-nitrobenzyl alcohol were incubated with male Fischer-344 rat hepatic cytosol and PAPS, microsomes and NADPH, or microsomes and cytosol with PAPS, NADPH, and acetyl coenzyme A. DNA was isolated and analyzed for radiolabel bound covalently. Analysis of the incubations containing [14C]-2-aminobenzyl alcohol revealed radiolabel bound covalently to DNA, as well as one major metabolite labile in both sulfatase and acid. The appearance of each required the presence of PAPS and cytosol and was inhibited by the sulfotransferase inhibitor 2,6-dichloro-4-nitrophenol. Neither NADPH nor acetyl coenzyme A played a role in the generation of detectable 14C bound to nucleic acids. 2-Amino-6-nitrobenzyl alcohol was converted to metabolites capable of binding to calf thymus DNA when incubated with cytosol and PAPS or with microsomes and NADPH. However, when cytosol and microsomes were incubated together, activation of 2-amino-6-nitrobenzyl alcohol appeared to require only PAPS, suggesting a minor role for NADPH-dependent enzymes in its activation. The results suggest that the metabolite of 2-nitrotoluene responsible for binding covalently to DNA is 2-aminobenzyl sulfate. There may be more than one pathway involved in the formation of metabolite(s) of 2,6-dinitrotoluene that bind covalently to DNA.
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PMID:In vitro activation of 2-aminobenzyl alcohol and 2-amino-6-nitrobenzyl alcohol, metabolites of 2-nitrotoluene and 2,6-dinitrotoluene. 251 19

3-Hydroxy-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (3-OH-BP-7,8-diol) was isolated from arylsulfatase/beta-glucuronidase-treated bile of rats to which 3-hydroxybenzo[a]pyrene (3-OH-BP) has been administered. This triol was investigated for mutagenicity in Salmonella typhimurium (reversion to histidine prototrophy of strains TA 97, TA 98, TA 100 and TA 1537) and in V79 Chinese hamster cells (acquisition of resistance to 6-thioguanine). When no exogenous metabolizing system was added the triol was inactive, while 3-OH-BP showed weak mutagenic effects with all four bacterial strains. In the presence of NADPH-fortified postmitochondrial supernatant fraction (S9 mix) of liver homogenate from Aroclor 1254-treated rats, the mutagenicity of 3-OH-BP was potentiated, and the triol was activated to a mutagen(s). In the presence of S9 mix, the triol was 5-18 times more mutagenic than 3-OH-BP in strains TA 97, TA 100 and TA 1537, but both compounds showed similar mutagenic potencies with strain TA 98. These strain differences strongly suggest that the mutagenicity of 3-OH-BP in the S9 mix-mediated test was not exclusively due to metabolites of 3-OH-BP-7,8-diol. Trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol), like the triol, showed mutagenic effects only in the presence of S9 mix. Strain TA 1537 was reverted by the triol but not by the diol. In the other bacterial strains the diol was more mutagenic than the triol, the difference in potency being largest in strain TA 100 (2.5- to 10-fold, depending on the experimental conditions). In V79 cells, the diol was a potent mutagen, while the triol showed only very weak mutagenic effects. However the triol was more cytotoxic than the diol. High cytotoxicity of the triol was observed even in the absence of S9 mix. The results of the present study demonstrate that metabolites of 3-OH-BP-7,8-diol are biologically-active derivatives of benzo[a]pyrene. Comparison of the mutagenic effectiveness in different bacterial strains also reveals that metabolites of 3-OH-BP-7,8-diol and of BP-7,8-diol substantially differ in the kind of genetic alterations they evoke.
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PMID:Metabolic activation to a mutagen of 3-hydroxy-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene, a secondary metabolite of benzo[a]pyrene. 331 46

The early primary biochemical response of lung to NO2 was studied separately from the later secondary responses of inflammation and proliferation by measuring several biochemical parameters in lungs of rats immediately following a 4-hr exposure to nitrogen dioxide (NO2) at concentrations of 10, 20, 30, and 40 ppm. Cell-free lavage fluid contained elevated amounts of lactate dehydrogenase (LDH), malate dehydrogenase (MDH), isocitrate dehydrogenase (IDH), glucose-6-phosphate dehydrogenase (GDH), acid phosphatase (AP), and aryl sulfatase (AS) after 30 or 40 ppm NO2. Total protein and sialic acid were increased in cell-free lavage after 20, 30, or 40 ppm NO2. The amounts of protein, sialic acid, and acid phosphatase recovered by airway lavage were equal to the amounts found in 0.7 ml of plasma, consistent with transudation of this volume of plasma into airways as a source of these parameters. The plasma activity of the other parameters measured was too low to account for their increase in lavage fluid by plasma leakage into airways. Decrease in the number and enzyme content of lavagable cells indicated damage to free cells in the airways. The amount of the decrease in enzyme content of the lavagable cell fraction was similar to the increase in the cell-free lavage for all of the measured enzymes except acid phosphatase, suggesting the release of these enzymes into airways as a result of damage to free cells. However, the LDH isoenzyme profile in cell-free lavage after exposure is inconsistent with free cells as the source of this enzyme. No changes were observed in the whole-lung homogenate content of protein, DNA, lipid, LDH, MDH, IDH, GDH, AP, AS, glutathione reductase, NADPH cytochrome c, or succinate cytochrome c reductase immediately after NO2 exposure. This study indicates that initial acute damage to lung by NO2 results in translocation of enzymes, proteins, and sialic acid into airways. Plasma is a likely source of translocated protein, sialic acid, and acid phosphatase. The sources of the other enzyme activities remain to be identified, with lung parenchyma and free cells as likely sources.
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PMID:Biochemical assessment of acute nitrogen dioxide toxicity in rat lung. 404 14

Toxicity tests on Culex pipiens fatigans with propoxur (o-isopropoxyphenyl methylcarbamate) and carbofuran (2,2-dimethyl-2,3-dihydrobenzofuranyl-7-methylcarbamate) indicated that both compounds are fast-acting insecticides. Transfer of treated larvae to fresh water results in their partial recovery from knockdown.Propoxur is metabolized by resistant and susceptible larvae by their homogenate-reduced nicotinamide-adenine dinucleotide phosphate (NADPH(2)) enzyme system and by the microsome-plus-soluble fraction of mouse-liver extracts to at least 10 organosoluble metabolites with the isopropoxy group intact. The major metabolites, which are primarily hydroxylation products or the result of degradation of these products, have tentatively been identified as: acetone plus o-hydroxyphenyl methylcarbamate, 2-isopropoxy-5-hydroxyphenyl methylcarbamate, 2-isopropoxyphenyl carbamate, and 2-isopropoxyphenyl N-hydroxymethylcarbamate. Upon incubation of water-soluble products from treated larvae with beta-glucosidase, beta-glucuronidase, aryl sulfatase and acid phosphatase, the conjugates are hydrolysed, liberating mainly hydroxylated carbamates.The results indicate that slower absorption as well as faster detoxification by hydroxylation mechanisms, together with conjugation with polar molecules and elimination, are major factors in resistance of mosquito larvae to substituted-aryl methylcarbamate insecticides.
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PMID:Carbamate resistance in mosquitos. The metabolism of propoxur by susceptible and resistant larvae of Culex pipiens fatigans. 531 55

The metabolism of endogenous estrogens, estradiol and estrone, and the irreversible binding of estrogens to cellular macromolecules have been examined and compared in subcellular microsomal and in intact hepatocyte preparations. In studies with rat liver microsomal preparations containing estradiol, an NADPH-generating system, and denatured DNA, the irreversible binding of radiolabeled steroid metabolite(s) to the microsomal proteins was 3.26 nmoles/mg protein in 1 hr (S.D. 0.39; 7.9% of total steroid) while binding to DNA was found to be 0.288 nmole/mg DNA/mg protein (S.D. 0.025; 0.39% of total steroid). No significant difference was observed between microsomal preparations from untreated, phenobarbital-treated or 3-methylcholanthrene-treated rats. Irreversible binding to proteins was also demonstrated in the intact hepatocyte cell incubations. After 2-hr incubations of estradiol with hepatocytes, 5.9% (S.D. 1.4%) of the steroid(s) was irreversibly associated with cellular proteins (approximately 1.43 pmoles/mg/min). Analysis of the organic-soluble metabolites demonstrated the presence of the catechol estrogens and their metabolites, 2-hydroxyestradiol, 2-hydroxyestrone, 2-methoxyestradiol, and 2-methoxyestrone. Estrone and estriol were also identified. The aqueous-soluble materials isolated from hepatocyte incubations contained glucuronide, sulfate, and apparent thioether conjugates, as determined by liberation from estrogen metabolites by treatment with beta-glucuronidase, sulfatase, and Raney nickel. Thus, extensive primary and secondary metabolism of estrogens occurs in intact hepatocyte incubations. Furthermore, irreversible binding of estrogens to cellular proteins occurs in these intact cells having demonstrated conjugative pathways of metabolism.
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PMID:Estrogen metabolism in rat liver microsomal and isolated hepatocyte preparations--I. Metabolite formation and irreversible binding to cellular macromolecules. 650 37


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