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

---

Query: EC:3.1.6.1 (sulfatase)
3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an effort to improve the precision in prenatal monitoring for metachromatic leukodystrophy, levels of cerebroside sulfatase were determined in fibroblasts and amniotic fluid cells. Cells from MLD patients demonstrated no significant sulfatide hydrolysis, whereas cultures from heterozygous subjects hydrolyzed diminished but definite amounts of sulfatide. Cells from a fetus with low arylsulfatase A activity were able to cleave considerable amounts of sulfatide; enzyme assays performed postnatally suggest that the infant is heterozygous for MLD. This report documents the value of cerebroside sulfatase assays in the in utero monitoring for MLD.
...
PMID:Cerebroside sulfatase activity in cultivated human skin fibroblasts and amniotic fluid cells;. 112 3

A 4-year old boy died of diffuse disseminated sclerosis (DDS) of the brain and was found to have also pseudoarylsulfatase A deficiency (PASAD) with about 20% residual arylsulfatase A (ASA) and cerebroside sulfatase (CS) activity. The reexamination of lipids did not show any sulfatide accumulation in the patient's organ extracts. Although the residual CS activity in the patient's extracts was clearly demonstrable only after partial purification, it was concluded that this activity protects organ tissues from sulfatide accumulation in PASAD, since in sulfatide lipidosis (metachromatic leukodystrophy, MLD) no residual CS activity was detectable. The study of residual ASA activity in the patient's fibroblasts by gel electrofocusing resulted in an almost normal enzyme microheterogeneity. However, the detailed study of the brain galactolipids in the patient revealed an elevated ratio of sulfatide/galactocerebroside content, despite the decrease of both lipids. In tissues of other patients with severe demyelinating diseases different from DDS and MLD, this galactolipid ratio was also found to be increased, especially in three patients with adrenoleukodystrophy. A general mechanism of this anomaly in severe demyelination is considered.
...
PMID:Brain galactolipid content in a patient with pseudoarylsulfatase A deficiency and coincidental diffuse disseminated sclerosis, and in patients with metachromatic, adreno-, and other leukodystrophies. 287 76

Arylsulfatase A hydrolyzes the artificial chromogenic substrate 4-nitrocatechol-sulfate at 0 degree C at a rate of 24% of that at 37 degrees C whereas arylsulfatase B is almost inactive at 0 degree C. Based on this observation, a simple assay was developed which permits the accurate determination of low residual arylsulfatase A activities in cultured skin fibroblasts of infantile, juvenile and adult MLD patients and pseudodeficient individuals. In cultured skin fibroblasts, the following residual activities were found with this assay system: late-infantile patients, 0.0%, one juvenile patient, 1.0%, adult patients, 4.4-14% of normal average. healthy pseudodeficient probands ranged between 18% and 32%.
...
PMID:A simple chromogenic assay for arylsulfatase A. 288 12

A simple procedure was developed to assay the ability of arylsulfatase A in extracts of cultured skin fibroblasts to degrade the natural substrate, sulfatide, in the presence of the physiological activator protein but without detergents. Inhibitory substances were removed by dialysis and by batch-wise ion-exchange chromatography. The enzyme recoveries during purification were monitored with a newly developed method that employs the chromogenic substrate 4-nitrocatecholsulfate at an incubation temperature of 4 degrees C. The residual sulfatidase activities determined with this procedure in fibroblasts from patients with various forms of MLD correlated well with the severity of the disease.
...
PMID:Assay for cerebroside sulfate (sulfatide) sulfatase in cultured skin fibroblasts with the natural activator protein. 288 46

Multiple-sulfatase deficiency (MSD) is now considered to be heterogeneous and could be classified into three or four clinical phenotypes according to the onset of the disease: neonatal, late infantile, juvenile and possibly adult type. Neonatal-type MSD shows severe clinical involvement and practically no arylsulfatase A, B and C activities in cultured skin fibroblasts. Furthermore, arylsulfatase A activity in neonatal-type MSD was not enhanced by the addition of thiosulfate. Therefore, it is distinct from late infantile-type MSD. The degradation of 14C-sulfatide can occur in MSD-cultured skin fibroblasts and was much higher than in late infantile-type MLD. The addition of thiol protease such as leupeptin to cultured MSD skin fibroblasts enhanced arylsulfatase A activity as well as the degradation of 14C-sulfatide. This suggests that the decreased activities of arylsulfatase A is due to an acceleration of the enzyme degradation. Enzyme replacement by the addition of arylsulfatases of different sources (human liver, brain, fungus) was carried out in cultured MSD skin fibroblasts. Human enzymes of arylsulfatase A and B were mostly taken up by MSD cells rather than those of fungus origin. By the exposure to leukocytes to cultured skin fibroblasts, MSD cells corrected arylsulfatase A and B activities.
...
PMID:Pathochemistry, pathogenesis and enzyme replacement in multiple-sulfatase deficiency. 289 4

Metachromatic leukodystrophy is the name given to a group of diseases in patients having a deficiency of CS sulfatase activity. The diagnosis usually can be made by using leukocytes, urine, and cultured skin fibroblasts. The low level of enzyme activity can be measured with an artificial substrate, NCS, or suitably labeled CS. In a number of families, healthy carriers of this autosomal recessive disease have been found to have enzyme levels near those of affected patients. We prepared (14)C-stearic acid-labeled CS and studied its metabolism in cultured human cells from patients and controls, In vitro, CS sulfatase requires bile salts to stimulate the enzymatic reaction. The (14)C-CS also can be added to the medium on cultured cells, and its metabolism in the cells can be followed without the addition of bile salts. A child with late infantile MLD was identified by studies on urine and leukocytes. Studies on leukocytes from the parents revealed a very low enzyme level in the father (false positive) and a typical carrier level in the mother. A pregnancy in this family was monitored, and in vitro studies on cultured AFC revealed low CS and NCS sulfatase levels. However, the addition of (14)C-CS to the culture medium revealed normal metabolism in these cells. An unaffected fetus was predicted on the basis of the cell feeding studies. The couple elected to abort this pregnancy, and studies on the fetus confirmed it would not have been affected with MLD.
...
PMID:Metabolism of fatty acid-labeled cerebroside sulfate in cultured cells from controls and metachromatic leukodystrophy patients. Use in the prenatal identification of a false positive fetus. 611 97

The intact fibroblast cerebroside sulfate loading test is useful because sulfatide hydrolysis can be demonstrated in late onset MLD cell types with 1% or less of normal arylsulfatase A. In such cells, hydrolysis of sulfatide was inhibited when the loading test was carried out in growth media containing the organic ampholyte Hepes. Since Hepes did not affect uptake of sulfatide nor intracellular levels of arylsulfatase A, it was concluded that Hepes inhibited sulfatide hydrolysis by increasing lysosomal pH. The cerebroside sulfate loading test in the presence of Hepes should be useful as a probe for arylsulfatase A dysfunction in atypical MLD fibroblasts.
...
PMID:Effect of Hepes on the fibroblast cerebroside sulfate loading test. 661 87

MLD is caused by a deficiency of arylsulfatase A and hence sulfolipids are accumulated in various patient's tissues. Various clinical phenotypes including activator deficiency, pseudodeficiency and MSD. Recently, molecular basis of these disorders have been identified. Clinical phenotype in MLD is well correlated with their genotype. Most common mutation in Caucasian MLD is caused by 609A mutation which produces late infantile MLD. In Japanese, most common mutation is 445A mutation. Essential treatment of MLD is recently carried out by bone marrow transplantation. On the hand, MSD is caused by multiple deficiencies of various sulfatases and hence accumulated various sulfated compounds such as sulfatide and acid mucopolysaccharides. The clinical features have combined characteristics of MLD and mucopolysaccharidosis. The cause of this disorder is recently identified as abnormal modification of various sulfatase.
...
PMID:[Metachromatic leukodystrophy (MLD) and Multiple sulphatase deficiency (MSD)]. 857 48

Multiple sulfatase deficiency (MSD, OMIM 272200) is an autosomal recessive leukodystrophy associated with the deficiency of several, in total seven, sulfatases. The disorder is clinically and biochemically variable. The clinical picture combines features of mucopolysaccharidosis and metachromatic leukodystrophy (MLD, OMIM 250100) in a variable spectrum. Here we report a 3-year old Iranian girl with an MLD-like presentation of MSD. Arylsulfatase A deficiency and sulfatide excretion were found. Differently from what was previously reported in the literature, this girl never showed abnormal mucopolysaccharide excretion in the urine. There were no additional visceral or skeletal signs. She was originally diagnosed as having MLD. Only when she developed ichthyosis were seven additional sulfatases measured. In leukocytes, arylsulfatase A, steroid sulfatase and N-acetylglucosamine-6 sulfatase were profoundly deficient, while iduronate-2 sulfatase and arylsulfatase B were moderately reduced. In fibroblasts, N-acetylglucosamine-6 sulfatase was deficient, while arylsulfatase A was moderately reduced. This case illustrates the possible pitfalls in the clinical and laboratory diagnosis of MSD.
...
PMID:Pitfalls in the diagnosis of multiple sulfatase deficiency. 1131

The inherited deficiency of arylsulfatase A (ASA) in humans causes lysosomal accumulation of sulfatides in visceral organs and in the nervous system and leads to wide-spread demyelination (metachromatic leukodystrophy, MLD). ASA-deficient mice have previously been generated by means of targeted gene disruption. In the present study, visceral organs of ASA-deficient mice were investigated. A simple technique for the histochemical detection of accumulated sulfatides was elaborated using pre-embedding staining with alcian blue. The gall bladder, intrahepatic bile ducts, exocrine pancreatic ducts, respiratory epithelium and, with low degree, testicular Sertoli cells, showed sulfolipid storage. The storage pattern in the kidney will be described in a separate publication. Hepatocytes, pancreatic islets, adrenal glands, and gastric epithelium were unaffected. Ultrastructurally, the intralysosomal storage material displayed parallel and concentric lamellar patterns. Apart from some differences, the topographic distribution of the sulfatide storage resembled that in human MLD. In addition to being an animal model of the human disease, the ASA-deficient mouse may be useful for investigating the cell biology of sulfolipids in visceral organs.
...
PMID:Sulfatide storage in visceral organs of arylsulfatase A-deficient mice. 1149 46


1 2 Next >>

---