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)

To see whether urine enzyme activities could be used as an index in evaluating the disease status of leukemia patients, we examined the activities of four enzymes: arylsulfatases A(AS-A) and B(AS-B), alkaline phosphatase (AP), and lactate dehydrogenase (LDH). AP and LDH showed no consistent patterns. The activities of AS-A and AS-B correlated well with the patient's clinical status, increasing during progression of disease and decreasing toward normal activities during responses to therapy, as judged from bone marrow cellularity and differential. Among 23 untreated patients with a histologic diagnosis of acute leukemia we found increased activities of the urine enzymes in these proportions: AS-A in 23 patients (100%), AS-B in 22 (95.7%), AP in 7 (30.4%), and LDH in 10 (43.5%). Five patients in remission from acute leukemia had normal activities for all four enzymes. In one patient in remission for more than one year, a rise in urinary arylsulfatase activity preceded observable bone marrow relapse by 4 months. Unlike that of serum of urine lysozyme and serum copper, the determination of urine arylsulfatase activities appears to be a consistent, useful indicator of response to antileukemic therapy. In contrast to the determination of polyamines, the quantitation of arylsulfatase activity is achieved with greater ease and with instrumentation available in most clinical laboratories.
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PMID:A noninvasive technique for monitoring response to chemotherapy in human acute leukemia. 3

A new method is described for the direct cytochemical demonstration of lysosomal arylsulfatases utilizing a synthetic substrate, 4-nitro-1,2-benzenediol mono(hydrogen sulfate), and a copper capture reaction. A small amount of Hatchett's brown (cupric ferrocyanide, Cu2Fe(CN)6-7 H2O) formed at the subcellular sites of copper capture is then utilized as a heterogeneous catalyst to effect the oxidative polymerization of 3,3'-diaminobenzidine which results in the formation of an insoluble, highly colored osmiophilic indamine polymer at the sites of enzymatic activity. The reaction product even at this stage prior to osmication is highly visible. It is readily seen with a light microscope in 50 mum sections of fixed tissues prepared with a mechanical chopper or in 10 micron cryostat sections treated for arylsulfatase activity. Upon osmication, an electron-opaque osmium black is formed which is much less soluble than the products of either the lead or barium capture reactions currently used for the demonstration of arylsulfatase with the electron microscope. The selection of areas of plastic-embedded tissues for ultrathin sectioning is facilitated by the ready visibility of these osmium black end products on 1-2 mum plastic sections which can be studied with the light microscope. This method gives permanent specimens demonstrating arylsulfatases A or B in lysosomes and autophagic vacuoles. In addition, enzyme activity is seen occasionally in the Golgi region or lamellae of certain cells believed to be elaborating sulfated products. In these instances, it may be demonstrating sulfotransferase activity.
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PMID:The demonstration of arylsulfatases with 4-nitro-1,2-benzenediol mono(hydrogen sulfate) by the formation of osmium blacks at the sites of copper capture. 4 59

Sodium/copper chlorophyllin (CHL) is a water-soluble derivative of chlorophyll that exhibits antimutagenic activity in several short-term genotoxicity assays and inhibits carcinogen-DNA binding in vivo. The effect of CHL pretreatment on the excretion of mutagens in the urine and feces of male Sprague-Dawley rats has been studied using the Salmonella mutagenicity assay. Animals were given 1 percent CHL in the drinking water for 2 days before administering a single dose of 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ) by oral gavage. Rats pretreated with CHL had higher levels of mutagens in the urine and feces compared with animals given IQ alone; 48 hr after IQ administration, the total mutagenic dose excreted was < 4% in controls vs. 18% in rats given CHL. Mutagenicity required the presence of an activation system, was unaffected by treatment with beta-glucuronidase or arylsulfatase, and in both the urine and feces was accounted for by increased elimination of unmetabolized parent compound. The results support the view that CHL may operate in vivo as a "desmutagen" or interceptor molecule, interacting with IQ in the gut and tissues, and reducing carcinogen bioavailability.
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PMID:Chlorophyllin-enhanced excretion of urinary and fecal mutagens in rats given 2-amino-3-methylimidazo[4,5-f]quinoline. 139 10

In research on congenital metabolic disorders, a biochemist can choose between the theoretical and the practical approach. The diagnosis of metabolic diseases relies on 1) the determination of the presence of metabolites under normal conditions that are direct substrates of the defective enzyme (e.g., the Gm2 ganglioside in the brain tissue of a patient with Tay-Sachs disease); 2) the determination of the lack or insufficiency of the direct product of the defective enzyme (e.g., aryl sulfatase A in the cells of patients with metachromatic leukodystrophy), hormone (hypothyroidism), or receptor (congenital hypercholesterolemia); 3) determination of substance whose reduction was established by experimentation, but the cause of the decrease is not known (ceruloplasmin in Wilson's disease); and 4) DNA analysis. Metabolic impairment of genetic origin is not treatable. The disease can be prevented by 1) removing the inappropriate metabolite (e.g., copper accumulation can be avoided by giving penicillamine or zinc salts); 2) limiting those substances in the critical phase of childhood that are components of the defective enzyme (e.g. gluten reduction in colic and protein in phenylketonuria); 3) supplementing the insufficient metabolite (e.g., phosphate in hypophosphatemia by sound for 12 hours a day); 4) protecting the patients (e.g. from light in porphyria); and 5) treatment by substances (giving coagulation factor VIII in hemophilia and thyroid hormones in hypothyroidism). There is a dilemma in subjecting patients to a diagnosis of progression to Huntington's chorea 20 years in advance or informing them about the high risk of hereditary disease for the next child (25% for the recessive and 50% for the dominant mode). Ethical committees have usually opted for a recommendation of selective abortion in clear-cut cases. Increasingly refined diagnostic methods have magnified the responsibility of the biochemist.
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PMID:[Prenatal diagnosis: a chance? risk? dilemma?]. 209 55

Iduronate sulfatase was purified from human liver for an investigation of the degradative pathway of dermatan sulfate. An overall 80-fold purification was achieved and, more importantly, the preparation was free of alpha-L-iduronidase, beta-glucuronidase, N-acetylgalactosamine 4-sulfate sulfatase (arylsulfatase B) and highly enriched in beta-N-acetylhexosaminidase. The liver enzyme appeared to be composed of several molecular species. The enzyme activity was optimal at pH 4.0 and its Km was 10--20 microM with sulfoiduronyl sulfoanhydromannitol. Chloride was inhibitory at high concentration and among divalent metal ions, only copper was inhibitory. Nitrocatechol sulfate was not a substrate, but did show competitive inhibition. Its Ki for iduronate sulfatase was similar to its Km for arylsulfatase, suggesting a similarity in the substrate binding sites of iduronate sulfatase and arylsulfatases.
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PMID:Purification and some properties of human liver iduronate sulfatase. 695 Sep 34

In Chlamydomonas reinhardtii, cytochrome c6 (cyt c6) is synthesized only under conditions of copper deficiency when plastocyanin cannot be synthesized. In previous work, the copper-responsive regulation of cyt c6 synthesis was demonstrated to occur by control of transcription, with no contribution from post-transcriptional processes. To understand the mechanism underlying its regulation, the genomic DNA encoding cyt c6 (Cyc6) was analyzed for the presence of copper-responsive elements. Sequences lying between positions -127 and -7 with respect to the start site of transcription were found to be sufficient to confer copper-responsive expression on either a promoterless or a minimal beta-tubulin promoter-driven (arylsulfatase-encoding) reporter gene. Analysis of this 120-bp fragment indicated that copper-responsive elements lie in two distinct regions (between -110 to -56 and -127 to -109). ATG fusions between copper-insensitive promoters and the coding plus 3' untranslated region of the Cyc6 gene resulted in the accumulation of cyt c6 in copper-supplemented medium; this confirms earlier studies indicating a lack of post-transcriptional control in this copper-responsive pathway. In the context of a constitutive promoter (derived from the beta-tubulin gene), each region was found to function as an activator of transcription in copper-deficient cells, and the metal specificity of the response of reporter genes containing either one or both regions was identical to that of the endogenous Cyc6 gene. The copper-responsive synthesis of cyt c6 is thus attributed to these two 5' upstream sequences.
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PMID:Two copper-responsive elements associated with the Chlamydomonas Cyc6 gene function as targets for transcriptional activators. 778 Mar 10

We have studied the intracellular fate of the apolipoprotein B of copper-oxidized LDL in cultured J774 macrophages, using subcellular fractionation and immunofluorescence techniques. The oxidized apolipoprotein B, using cell fractionation, was located primarily in secondary lysosomes (identified using the lysosomal marker-enzyme aryl sulfatase). Light microscopy using antibodies to the mannose-6-phosphate receptor, the lysosomal membrane protein lgp 120, and oxidized LDL (biotinylated) confirmed that apo B of oxidized LDL did accumulate in secondary lysosomes rather than in endosomes. We conclude from these results that the oxidized apolipoprotein B of LDL reaches the secondary lysosomes, but is not efficiently degraded, leading to intracellular accumulation within this compartment. If this occurs in vivo it may influence the physiology of the macrophage and their subsequent roles in forming foam cells and the development of the fatty streaks of early atherosclerosis.
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PMID:Apolipoprotein B of oxidized LDL accumulates in the lysosomes of macrophages. 815 30

The effect of a single oral administration of proanthocyanidins, oligomeric and polymeric polyhydroxyflavan-3-ol units, on the antioxidative potential of blood plasma was studied in rats. Proanthocyanidin-rich extract from grape seeds was administered by intragastric intubation to fasted rats at 250 mg/kg of body weight. The plasma obtained from water- or proanthocyanidin-administered rats was oxidized by incubation with copper sulfate or 2, 2'-azobis(2-amidinopropane) dihydrochloride (AAPH) at 37 degrees C, and the formation of cholesteryl ester hydroperoxides (CE-OOH) was followed. The plasma obtained from proanthocyanidin-administered rats was significantly more resistant against both copper ion-induced and AAPH-induced formation of CE-OOH than that from control rats. The lag phase in the copper ion-induced oxidation of rat plasma was remarkably increased at 15 min after administration of proanthocyanidins and reached a maximum level at 30 min. When the plasma from proanthocyanidin-administered rat was hydrolyzed by sulfatase and beta-glucuronidase following analysis by high-performance liquid chromatography with electrochemical detection, metabolites of proanthocyanidins occurred in rat plasma at 15 min after administration, three peaks of which were identified as gallic acid, (+)-catechin, and (-)-epicatechin. These results suggest that the intake of proanthocyanidins, the major polyphenols in red wine, increases the resistance of blood plasma against oxidative stress and may contribute to physiological functions of plant food including wine through their in vivo antioxidative ability.
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PMID:Increase of antioxidative potential of rat plasma by oral administration of proanthocyanidin-rich extract from grape seeds. 1055 67

Quercetin is a typical flavonoid present mostly as glycosides in plant foods; it has attracted much attention for its potential beneficial effects in disease prevention. In this study, we examined human volunteers after the short-term ingestion of onion, a vegetable rich in quercetin glucosides. The subjects were served diets containing onion slices (quercetin equivalent: 67.6-93.6 mg/day) with meals for 1 wk. Quercetin was only found in glucuronidase-sulfatase-treated plasma, and its concentration after 10 h of fasting increased from 0.04 +/- 0.04 microM before the trial to 0.63 +/- 0.72 microM after the 1-wk trial. The quercetin content in low-density lipoprotein (LDL) after glucuronidase-sulfatase treatment corresponded to <1% of the alpha-tocopherol content. Human LDL isolated from the plasma after the trial showed little improvement of its resistance to copper ion-induced oxidation. It is therefore concluded that conjugated metabolites of quercetin accumulate exclusively in human blood plasma in the concentration range of 10(-7) approximately 10(-6) M after the short-term ingestion of vegetables rich in quercetin glucosides, although these metabolites are hardly incorporated into plasma LDL.
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PMID:Accumulation of quercetin conjugates in blood plasma after the short-term ingestion of onion by women. 1093 33

Tetrahydrocurcumin (THC) is an antioxidative substance which is derived from curcumin by hydrogenation. Curcumin is the main component of turmeric and is responsible for the yellow color of curried foods.First, LDL derived from a normal human volunteer was incubated in the presence of an antioxidant with 10 microM CuSO(4) at 37 degrees C for 2 hours.All antioxidants tested (THC, curcumin, probucol, and alpha-tocopherol) dose-dependently (1-10 microM) inhibited the oxidative modification of LDL. Probucol was the strongest, followed by THC, alpha-tocopherol, and curcumin.Next, in order to evaluate the antioxidative activity of THC in vivo, we fed rabbits diets containing 1% cholesterol with or without 0.5% THC and examined their effects on oxidative stress and atherosclerosis. Animals were divided into two groups: the control group rabbits (n = 12) were fed a normal chow diet and the experimental group (n = 12) was fed a diet containing 0.5% THC for one week.Then, 1% cholesterol was added to the diets and the animals were allowed to feed further for either 6 (n = 4 for each group) or 12 weeks (n = 8 for each group). Although serum cholesterol levels rapidly increased after starting the high cholesterol diet, no difference was observed between the control and THC groups.TBARS formation in the absence of added copper ion was inhibited in the LDL separated from THC-treated animals compared with that from control animals.THC treatment tended to inhibit the area covered with atherosclerotic lesions compared with the control, although this was not significant (28.8 +/- 17.5% vs. 40.0 +/- 23.7%, p = 0.2). Formation of N(epsilon)-(hexanoyl) lysine, 4-hydroxynonenal and dityrosine in liver and kidney also had a tendency to be inhibited by THC treatment. Although free THC was not detected in serum and liver, THC was detected in samples treated with beta-glucuronidase and sulfatase, suggesting that THC is present as a conjugate with glucuronic acid or sulfate. In conclusion, the present results suggest that curcuminoids, particularly THC, which are contained in turmeric, may be useful as a functional food factor.
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PMID:The protective effects of tetrahydrocurcumin on oxidative stress in cholesterol-fed rabbits. 1240 34


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