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)

We have assessed the effectiveness of transplanted histocompatible fibroblasts as a long-lived source of lysosomal enzymes for replacement therapy in three patients with Hunter's syndrome, over periods ranging from 2.5 to 3.75 yr. The level of Hunter corrective factor excreted by all three patients increased after transplantation, as did the activity of alpha-L-idurono-2-sulfate sulfatase in serum, when measured directly with a radioactive disulfated disaccharide substrate. Sulfatase activity was also raised in leukocyte homogenates from the two patients that we were able to assess. These increases in enzyme activity were accompanied by corresponding increases in catabolism of heparan and dermatan sulfates, as shown by (a) a decrease in sulfate:uronic ratios of urinary oligosaccharides, (b) an increase in iduronic acid monosaccharide, and (c) a normalization of Bio-Gel P-2 gel filtration profiles. Both the increase in enzyme activity and increased catabolism were maintained during the period of study and were not affected by either a gradual decrease or total withdrawal of immunosuppressive therapy.
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PMID:Enzyme replacement therapy by fibroblast transplantation: long-term biochemical study in three cases of Hunter's syndrome. 10 13

Iduronate sulfatase, the enzyme deficient in Hunter syndrome, can be readily measured in individual hair roots. Samples from Hunter syndrome hemizygotes had activities at or near the limits of detection. Samples from two mothers of Hunter syndrome patients, one an obligate heterozygote, had lower average iduronate sulfatase activity than the normal mean, and a significant number of hair roots had activity in the pathognomic range. A third mother showed a normal distribution of enzyme activity, and no hair roots were in the range of those from an affected individual. These results are similar to studies on the distribution of other X-linked enzymes in individual hair root samples from heterozygotes. This suggests that hair root iduronate sulfatase assessment is useful in the detection of Hunter syndrome carrier status, but further refinement of the test system is necessary.
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PMID:Iduronate sulfatase analysis of hair roots for identification of Hunter syndrome heterozygotes. 10 23

Cultured fibroblasts from two individuals with multiple sulfatase deficiency (MSD) were found to have decreased activities of arylsulfatases (aryl-sulfate sulfohydrolase, EC 3.1.6.1) A, B, and C as well as iduronate-sulfate sulfatase, sulfamidase, and N-acetylglucosamine-6-sulfate sulfatase. The activity of N-acetylgalactosamine-6-sulfate sulfatase was decreased in one line but not in the other. Mixtures of MSD cell extracts with extracts from normal cells did not result in inhibition of normal sulfatase activities. Mixtures of MSD cell extracts with extracts of fibroblasts from patients with Hunter or Sanfilippo A syndrome did not activate iduronate-sulfate sulfatase or sulfamidase activity. Heterokaryons formed by fusion of MSD cells with Sanfilippo A fibroblasts demonstrated a partial correction of the enzyme deficiency. In similar manner, MSD-Hunter heterokaryons showed a significant increase in iduronate-sulfate-sulfatase activity. Genetic complementation in heterokaryons of MSD fibroblasts and cells of either Sanfilippo A or Hunter syndrome implies a genetic defect in MSD different from that causing specific sulfatase deficiencies.
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PMID:Genetic complementation studies of multiple sulfatase deficiency. 11 67

Using an assay for sulfoiduronate sulfatase based on the degradation of 35S mucopolysaccharides in a cell-free system, two clonal populations have been demonstrated in fibroblasts of heterozygotes for Hunter's syndrome. The locus responsible for sulfoiduronate sulfatase deficiency in this X-linked mucopolysaccharidosis is therefore subjected to dosage compensation in females.
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PMID:Mosaicism for sulfoiduronate sulfatase deficiency in carriers of Hunter's syndrome. 81 29

A female child of healthy, unrelated parents presented at 12 months of age with a history of moderately severe developmental delay, macrocephaly, dysmorphic facies, hypotonia, hepatosplenomegaly, mild generalized dysostosis multiplex, mucopolysacchariduria (dermatan and heparan sulfates), and Alder-Reilly bodies in peripheral blood leukocytes. Iduronate sulfatase activity in plasma was markedly depressed: 0.11 units/ml/h (normal, 1.75 +/- 0.56, N = 6). Analyses of arylsulfatases A, B, and C, heparan N-sulfatase, alpha-mannosidase, beta-mannosidase, beta-glucuronidase, beta-hexosaminidase, beta-galactosidase, and alpha-fucosidase activities in plasma, leukocytes, and/or cultured skin fibroblasts were all normal. Urinary sulfatide excretion was also within normal limits. Karyotypes of peripheral blood leukocytes and cultured skin fibroblasts were normal. Serum iduronate sulfatase activities in the parents were in the normal range (father, 1.63 units/ml/h; mother, 1.25 units/ml/h). The results of analyses of restriction fragment length polymorphisms (RFLP) of DNA from cultured skin fibroblasts with the use of probes for loci extending from Xpter to Xq28 showed X chromosome heterozygosity and confirmed the paternal origin of one of the X chromosomes. Studies on sulfur-35 uptake in mixed fibroblast cultures showed cross-correction of [35S]-glycosaminoglycan accumulation between cells from the patient and normal cells or cells from a patient with Hurler disease; however, there was no cross-correction between cells from the patient and those from boys affected with classical Hunter disease. This represents only the second confirmed case of Hunter disease reported in a karyotypically normal girl.
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PMID:Hunter disease (mucopolysaccharidosis type II) in a karyotypically normal girl. 211 88

Iduronate 2-sulfatase (IDS, EC 3.1.6.13) is required for the lysosomal degradation of heparan sulfate and dermatan sulfate. Mutations causing IDS deficiency in humans result in the lysosomal storage of these glycosaminoglycans and Hunter syndrome, an X chromosome-linked disease. We have isolated and sequenced a 2.3-kilobase cDNA clone coding for the entire sequence of human IDS. Analysis of the deduced 550-amino acid IDS precursor sequence indicates that IDS has a 25-amino acid amino-terminal signal sequence, followed by 8 amino acids that are removed from the proprotein. An internal proteolytic cleavage occurs to produce the mature IDS present in human liver shown to contain a 42-kDa polypeptide N-terminal to a 14-kDa polypeptide. The IDS sequence has strong sequence homology with other sulfatases (such as sea urchin arylsulfatase, human arylsulfatases A, B, and C, and human glucosamine 6-sulfatase), suggesting that the sulfatases comprise an evolutionarily related family of genes that arose by gene duplication and divergent evolution. The arylsulfatases have a greater homology with each other than with the non-arylsulfatases (IDS and glucosamine 6-sulfatase). The IDS cDNA detected RNA species of 5.7, 5.4, 2.1, and 1.4 kilobases in human placental RNA and revealed structural alterations and gross deletions of the IDS gene in many of the clinically severe Hunter syndrome patients studied.
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PMID:Hunter syndrome: isolation of an iduronate-2-sulfatase cDNA clone and analysis of patient DNA. 212 63

Iduronate sulfate sulfatase (ISS), the deficient hydrolase in Hunter syndrome, consistently increases in the serum of pregnant women, reaching a three- to fourfold increase from pre-pregnancy levels toward the end of pregnancy. In Hunter carriers, a correlation occurs between the status of the fetus with regard to Hunter syndrome and the ISS increase in maternal serum. Thus, in pregnancies with Hunter-affected fetuses, enzyme levels did not change in the serum of heterozygous mothers until abortion was performed, while in nonaffected fetuses, ISS increased usually very early in pregnancy--as early as the 6th-12th week. In heterozygote female fetuses, this increase might be delayed. These data imply that a prenatal diagnosis of Hunter syndrome might be accomplished in maternal serum at early conventional procedures for the prenatal diagnosis of Hunter syndrome.
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PMID:Hunter syndrome: prenatal diagnosis in maternal serum. 308 Aug 75

Skin fibroblasts cultured from patients affected with the Hunter syndrome are deficient in the activity of a protein, named the "Hunter corrective factor," that is required for degradation of dermatan and heparan sulfates. We now show that this factor, purified from human urine, removes about 2% of the sulfate residues from [(35)S]mucopolysaccharide accumulated within Hunter fibroblasts; these groups are derived from "oversulfated" regions of the polymer. Acetone-powder extracts of fibroblasts derived from patients with the Hunter syndrome are deficient in this sulfatase, in contrast to similar extracts from fibroblasts of individuals of other genotype. Hunter corrective factor coupled to alpha-L-iduronidase (or alternatively, mixed extracts from Hurler and Hunter fibroblasts) release iduronic acid from 4-O-alpha-L-sulfoiduronosyl-D-sulfoanhydromannose. We conclude that the Hunter corrective factor is a sulfatase for sulfated iduronic acid residues.
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PMID:The defect in the Hunter syndrome: deficiency of sulfoiduronate sulfatase. 426 73

Iduronate sulfate sulfatase activity was determined in 36 women, relatives of Hunter syndrome patients. The use of serum and lymphocyte extracts for the determination of enzyme levels enabled the detection of 13 out of 15 (86%) obligate heterozygotes and identification of 10 of 21 other relatives as carriers. These methods are relatively simple and can easily be applied for routine examinations of all women at risk of being a Hunter heterozygote. These results permit for the first time meaningful genetic counseling for the families of Hunter patients.
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PMID:Heterozygote detection in Hunter syndrome. 642 73

A prenatal diagnosis of Mucopolysaccharidosis II (M. Hunter) was made early in a pregnancy at risk in a family with one affected child. An affected fetus was diagnosed on the basis of an abnormal incorporation and degradation of 35SO4 in 35SO4-labeled mucopolysaccharides in cultured amniotic cells. Dermatan sulfate and heparin sulfate concentrations in the supernatant of the amniotic fluid were high. In the aborted fetus, the diagnosis could be confirmed by 35SO4 incorporation studies in the cultured fibroblasts and in cultured brain cells as well as by the deficiency of the specific enzyme activity (iduronide sulfate sulfatase) in the organs of the fetus. beta-Galactosidase was in the low normal range in liver and spleen but significantly reduced in brain. Under electron microscopy, the mesenchymal cells of liver and spleen showed lysosomal storage of material, presumably mucopolysaccharides, in excess of normal. In the neurons of the spinal ganglia and spinal cord, "Zebra bodies" in statu nascendi were observed.
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PMID:Prenatal mucopolysaccharidosis II (Hunter): a pathogenetic study. 677 Mar 31


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