Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

A large portion of the dose of propranolol in animals and man is unaccounted for. Using radiotracer and HPLC techniques, five previously unrecognized polar and labile metabolites were found in dog urine, together accounting for 34% of the urinary radioactivity. The two main metabolites, peak 2 (7% of the radioactivity) and peak 4 (17%) could be isolated and purified by butanol extraction and reversed phase HPLC. Direct probe MS analysis of the main peak 4 and GC/MS analysis of the same peak after trifluoroacetylation both yielded 4-hydroxypropranolol. These observations together with UV spectra before and after acid hydrolysis indicated peak 4 to be an acid- and heat-labile conjugate of 4-hydroxypropranolol with the conjugating group at the phenolic oxygen atom. Arylsulfatase from Helix pomatia and Aerobacter aerogenes completely hydrolyzed peak 4 to 4-hydroxypropranolol. Urine and plasma as well as the antioxidant sodium bisulfite, however, markedly inhibited the arylsulfatase activity. After conversion of peak 4 to its sodium salt, a fast atom bombardment-positive ion mass spectrum confirmed this metabolite to be the sulfate ester of 4-hydroxypropranolol, clearly demonstrating the quasimolecular ion (M + H)+ at m/z 378 as well as fragmentation with loss of the sulfate moiety. The second largest unknown metabolite in the dog, peak 2, was identified as the sulfate ester of 4-hydroxypropranolol glycol. The 4-hydroxypropranolol sulfate was also identified in both urine and plasma of a patient treated with propranolol, accounting for approximately 18% of the dose.
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PMID:Identification of major sulfate conjugates in the metabolism of propranolol in dog and man. 613 41

Metaproterenol (1-(3,5-dihydroxyphenyl)-2-isopropylaminoethanol) is primarily converted in humans to metaproterenol-3-O-sulfate following oral administration. Ion exchange column chromatography with a gradient of ammonium acetate buffer permitted the isolation of the ammonium salt of metaproterenol-3-O-sulfate from human urine. Treatment of aliquots of the column eluate with purified sulfatase and subsequent HPLC/fluorescence analysis confirmed the presence of metaproterenol. Comparison of the column eluate with a metaproterenol standard by 250-MHz proton-NMR revealed a pattern consistent with monosubstitution of the resorcinol ring. Negative and positive ion fast atom bombardment/mass spectrometry showed the metabolite to have a (M-H)- m/z of 290 and a (M + H)+ m/z ion of 292. These three methods support the structural assignment of metaproterenol-3-O-sulfate. Enzymatic hydrolysis of urine specimens from 29 different subjects with purified beta-glucuronidase as well as beta-glucuronidase-sulfatase mixtures yielded no significant increase in metaproterenol beyond purified sulfatase-treated urine, thus ruling out the presence of a glucuronide of metaproterenol. Approximately 40% of an oral 20-mg dose, given as either a tablet or a solution, was recovered in the urine as metaproterenol-3-O-sulfate. Approximately 5% of the dose was recovered in the unconjugated form. The majority of the dose was excreted over the first 12 hr with a biological half-life of 5-6 hr followed by a slower excretion phase with a half-life of 20 hr.
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PMID:Isolation and characterization of metaproterenol-3-O-sulfate: a conjugate of metaproterenol in human urine. 614 Jan 41

Most of the available histochemical methods and techniques (azodye, metal salt and indigogenic methods, cryostat, free-floating and lyophilized section techniques) and different modifications of these methods (different substrate concentrations, pH, temperature, incubation time e.g.) were applied to study the distribution of acid phosphatase (AcPB = after Barka and Anderson; AcPG = after Gomori), beta-glucuronidase (beta-Glu), aryl sulfatase (AS), beta-N-acetylglucosaminidase (NAG), acid 5'-nucleotidase (a5-Nucl), non-specific esterase (NE) and alkaline phosphatase (AlP) in the kidneys of rats of both sexes. The optimal conditions for the demonstration of these enzymes were established. As most important proved: the incubation of free-floating sections cut from "standard"-fixed (2 h in formol-calcium continued for another 18-22 h in the same fixative plus 0.88 M sucrose at 4 degrees C) kidney slices - only for AcPB and NE material fixed after Holt had to be used; the incubation for AlP and NE at 4 degrees C; final pH of the incubation medium for AcPB 5.5, AcPG 5.0 and NE 6.5; the use of Fast Garnet GBC Salt as coupler in the NE azo-dye reaction. Sex differences and for the female rats an increased activity during oestrus were established for all hydrolases studied. In particular the following results were obtained: AcPB, a5-Nucl and A1P are more intensive in male and AcPG in female S1 segments of the juxtamedullary nephrons in relation to the nephrons of the other parts of the cortex. In the medullary rays the NE and the a5-Nucl show a higher activity in the S2 segments of female rats demonstrate a more intensive activity for NAG and NE. This is true for AcPG and A1P in male rats. In the inner medulla a stronger beta-Glu activity in male rats and a stronger NAG activity in female rats is observed. The AcPB activity of the cortical distal tubules is higher in male rats.
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PMID:[Distribution of some hydrolases in the rat kidney (author's transl)]. 626 81

Dependence on the salt concentration of the activity of microsome-bound arylsulfatase C [EC 3.1.6.1] from rat liver was examined. The activity increased with increasing salt concentration in the reaction medium in the whole pH range tested. This effect can be explained by the dependence of the reaction rate on the surface pH and the surface concentration of the ionic substrate. The dependence on salt concentration of the activity of the microsome-bound arylsulfatase C and the pH-dependences of Vmax and Km of the enzyme were used for the estimation of pH at the microsomal surface. The two values of the surface pH (surface potential) and the salt concentration were applied to the Gouy-Chapman equation. The value of -0.39 +/- 0.08 X 10(-3) elementary charge/A2 was obtained as the surface charge density in the vicinity of the microsome-bound arylsulfatase C. This was smaller than the over-all value for microsomes (-1.08 +/- 0.04 X 10(-3) elementary charge/A2; Masamoto, K. (1982) J. Biochem. 92, 365-371). This suggests that the anion concentration in the vicinity of the enzyme on microsomes is lower than that in the bulk aqueous phase and is higher than the average value at the microsomal surface when the salt concentration is low.
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PMID:Dependence on surface pH and surface substrate concentration of activity of microsome-bound arylsulfatase C and the surface charge density in the vicinity of the enzyme. 658 19

Desulfation of bile acid 3-, 7- and 12-monosulfates was studied in incubates of fecal flora of man, rat and mouse. In anaerobic incubates, the 3 alpha-sulfates of the 5 beta-bile acids chenodeoxycholic acid and cholic acid, as well as the 3 alpha-sulfate of the 5 alpha-bile acid allochenodeoxycholic acid, were desulfated and further metabolized with the formation of a variety of metabolites. Desulfation yields were low in aerobically incubated samples, and aerobic subcultures were always negative. The 7- or 12-monosulfate esters of chenodeoxycholic acid and cholic acid were not hydrolyzed, neither anaerobically nor aerobically. High numbers (10(7) per 10(9) total count) of bile salt 3-sulfatase producing bacteria were present in rat cecal contents. No desulfating bacteria were detected in the proximal or medium small intestine of the rat, whereas low numbers were found in 2 out of 5 samples from the distal small intestine. These results reflect the predominantly anaerobic character of the bile salt sulfatase producing microflora in the intestine and suggest that the intestinal microflora of man, rat and mouse do not possess bile salt 7- or 12-sulfatase activity.
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PMID:Specificity of bile salt sulfatase activity in man, mouse and rat intestinal microflora. 670 61

A simultaneous azo-coupling method for the histochemical localization of d-equilenin sulfatase is described. d-Equilenin is a natural estrogenic steroid hormone, and its sulfuric acid ester was synthesized. It was found that the d-equilenin liberated during hydrolysis of d-equilenin sulfate by tissue sulfatase could be coupled with a diazonium salt to produce a purple precipitate indicating enzyme activity. d-Equilenin sulfatase was found in human tissues, but not in tissues of the rat. The optimum substrate concentration was 0.8 mM, activity was demonstrable over the wide pH range 5.0-8.0. Enzyme activity localized diffusely in the cytoplasm in optimally fixed specimens. Enzyme activity was also fairly well demonstrable in unfixed cryostat sections. Enzyme activity was completely inhibited by 0.1 M phosphate, 1 mM sodium tetraborate, 1 mM p-nitrophenyl sulfate and by 2 mM p-nitrocatechol sulfate. Estrone sulfate at concentration 0.8 mM had no effect, but at 4 mM caused marked inhibition of the reaction. At the same concentrations dehydroepiandrosterone sulfate did not inhibit the reaction. The chemical properties and tissue localizations of d-equilenin sulfatase differed from the properties of arylsulfatases A, B and C and other steroid sulfatases reported previously in the literature.
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PMID:Simultaneous azo-coupling method for an estrogen sulfatase in human tissues. 687 24

Bile acid sulfates, formed in human and rat livers, are desulfated by the intestinal microflora. In our study we first isolated from conventional rat feces an unnamed bacterium, termed strain S1, which desulfated the 5 beta-bile salt 3 alpha-sulfates in vitro and in vivo after association with gnotobiotic rats. Strain S1 also possessed 12 alpha-hydroxysteroid dehydrogenase and bile salt-deconjugating activities. The strain was a strict anaerobic, CO2-requiring, gram-negative, sporeforming rod and was designated as belonging to the genus Clostridium. Growth was scarce in culture media, unless in the presence of 0.1% taurine, a sulfur-containing amino acid. Addition of this substance raised the number of bacteria in thioglycolate and peptone yeast media from 10(4) per ml to 10(6) to 10(7) per ml and increased the colony diameter on agar medium from 0.2 mm to 0.5 to 0.9 mm. Sulfatase activity was specific for the 5 beta-bile salt sulfates, leaving the 5 alpha-bile salt sulfates unchanged. In addition, the sulfatase activity was cell bound, and its production was dependent on the composition of the culture medium, although no minimal sulfur medium was required for sulfatase activity.
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PMID:Isolation of a bile salt sulfatase-producing Clostridium strain from rat intestinal microflora. 705 72

A number of arylamines (including tyramine and tryptamine) increased the in vitro activity of arylsulfatase from Pseudomonas sp. strain C12B. Amino acid analogs of these amines (e.g., tyrosine and tryptophan) failed to exert an effect. Stimulation of activity by tyramine could not be accounted for in terms of sulfotransferase activity for this phenol, and no shift in the pH optimum for the enzyme occurred in the presence of tryptamine. Increased Vmax due to these amines was independent of enzyme concentration but varied significantly with substrate concentration. Evidence is presented which suggests that arylamines enhance arylsulfatase activity by forming a salt linkage with the substrate and rendering it more susceptible to enzymatic and acid-catalyzed hydrolyses. The recrystallized tryptamine salt of the substrate exhibited a reduced affinity for the enzyme but was hydrolyzed more rapidly than the potassium salt, which is normally employed as the assay substrate.
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PMID:Stimulation of bacterial arylsulfatase activity by arylamines: evidence for substrate activation. 724 96

To elucidate the chemical structure of slow-reacting substance of anaphylaxis from rat (SRS-A rat), SRS-A rat were purified by the method of Orange with modification using DEAE-Sephadex A-25 chromatography. Ultraviolet absorption spectrum of purified SRS-A rat indicated the presence of conjugated triene. Arylsulfatase B degradation products and HCl degradation products were subjected to analysis by a gas chromatography and mass spectrometry and a thin layer chromatography. Products obtained by arylsulfatase b catalysis contained 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid. HCl degradation products showed the presence of glycine, glutamic acid and cysteic acid. Furthermore, the analysis of anhydrous hydrazine degradation products of SRS-A rat and of HCl hydrolyzed products of dinitrophenylated SRS-A rat revealed the presence of glycine at C-terminal and glutamine acid at N-terminal. The study of the substrate specificity of arylsulfatase B against various materials including SRS-A rat suggested the presence of sulfone in SRS-A rat. The molecular ion peak of SRS-A rat sodium salt was observed at m/e 680 in field desorption mass spectrum of SRS-A rat. On the basis of these data, we identified the structure of SRS-A rat as [gamma]glutamyl-4(5-hydroxy-7,9,11,14-eicosatetraenoic acid-6-yl)-4,4-dioxyocysteinyl] glycine.
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PMID:Structure of slow-reacting substance of anaphylaxis (SRS-A). 746 61

Steroid sulfatases are responsible for the hydrolysis of 3beta-hydroxy steroid sulfates, such as cholesterol and pregnenolone sulfate, and have an important role in regulating the synthesis of estrogenic steroids, from estrone sulfate and dehydroepiandrosterone sulfate, in endocrine-dependent tumors. Although little is known about the mechanism by which the sulfate group is removed from a steroid nucleus, an active site-directed sulfatase inhibitor has been developed. This inhibitor, estrone-3-O-sulfamate (EMATE), was synthesized by treating the sodium salt of estrone with sulfamoyl chloride. This compound inhibited not only estrone sulfatase but also dehydroepiandrosterone sulfatase activity in placental microsomes and in intact MCF-7 breast cancer cells. Pretreatment of MCF-7 cells or placental microsomes with EMATE, followed by extensive washing or dialysis indicated irreversible inhibition. This was confirmed by showing that EMATE inhibited estrone sulfatase activity in placental microsomes in a time-, concentration-, and pH-dependent manner. The enzyme is protected from inactivation by estrone sulfate, which is also consistent with active site-directed inhibition. EMATE is proposed to inactivate estrone sulfatase by irreversible sulfamoylation of the enzyme. Maximum enzyme activity was detected at pH 8.6, and the maximum rate of enzyme inactivation by EMATE also occurred at this pH. The pKa values of the enzymatic reaction and pKa of inactivation were 7.2 and 9.8, providing evidence that two active site residues are being modified by EMATE. As the phenolic pKa of tyrosine (9.7) and the pKa of histidine will allow the roles that (6.8) are similar to the pKa values of inactivation, these amino acid residues may play a role in the catalytic mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inactivation of steroid sulfatase by an active site-directed inhibitor, estrone-3-O-sulfamate. 754 80


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