Morquio's syndrome: Deficiency of a chondroitin sulfate N-acetylhexosamine sulfate sulfatase

Matalon, Reuben; Arbogast, Bradley W.; Justice, Parvin; Brandt, Ira K.; Dorfman, Albert

doi:10.1016/0006-291x(74)91022-5

Cited by 127 publications

(43 citation statements)

References 5 publications

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“…Indeed, the KS urinary excretion of a 16-year-old female galactosialidosis patient was elevated at the level of 2.1 mg/24 h, similar to that of MPS IV type A patients (1.8 -2.4 mg/24 h; normal Ͻ 0.8 mg/24 h). 2 On the other hand, in fibroblasts of NEUR-deficient patients, which do not accumulate KS (28), the 1.27-MDa complex was present, and the amount of complex-bound GALNS corresponded to those in the control fibroblasts (Fig. 4d, peak I).…”

Section: Resultsmentioning

confidence: 88%

“…The cells were cultured in Eagle's minimal essential medium (Mediatech, Washington, D. C.), supplemented with 20% (v/v) fetal calf serum and antibiotics in 150-cm 2 Falcon flasks up to confluence (2-4 mg of protein/flask). The cells from one flask were harvested by trypsinization, rinsed with saline, sonicated in 1-2 ml of distilled water (5 s at 60 watts, twice), and assayed for enzyme activities as described above.…”

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confidence: 99%

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Association of N-Acetylgalactosamine-6-sulfate Sulfatase with the Multienzyme Lysosomal Complex of β-Galactosidase, Cathepsin A, and Neuraminidase

Pshezhetsky

Potier

1996

Journal of Biological Chemistry

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N-Acetylgalactosamine-6-sulfate sulfatase (GALNS) catalyzes the first step of intralysosomal keratan sulfate (KS) catabolism. In Morquio type A syndrome GALNS deficiency causes the accumulation of KS in tissues and results in generalized skeletal dysplasia in affected patients. We show that in normal cells GALNS is in a 1.27-MDa complex with three other lysosomal hydrolases: ␤-galactosidase, ␣-neuraminidase, and cathepsin A (protective protein). GALNS copurifies with the complex by different chromatography techniques: affinity chromatography on both cathepsin A-binding and ␤-galactosidase-binding columns, gel filtration, and chromatofocusing. Anti-human cathepsin A rabbit antiserum coprecipitates GALNS together with cathepsin A, ␤-galactosidase, and ␣-neuraminidase in both a purified preparation of the 1.27-MDa complex and crude glycoprotein fraction from human placenta extract. Gel filtration analysis of fibroblast extracts of patients deficient in either ␤-galactosidase (␤-galactosidosis) or cathepsin A (galactosialidosis), which accumulate KS, demonstrates that the 1.27-MDa complex is disrupted and that GALNS is present only in free homodimeric form. The GALNS activity and cross-reacting material are reduced in the fibroblasts of patients affected with galactosialidosis, indicating that the complex with cathepsin A may protect GALNS in the lysosome. We suggest that the 1.27-MDa complex of lysosomal hydrolases is essential for KS catabolism and that the disruption of this complex may be responsible for the KS accumulation in ␤-galactosidosis and galactosialidosis patients.

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Section: Resultsmentioning

confidence: 88%

mentioning

confidence: 99%

Association of N-Acetylgalactosamine-6-sulfate Sulfatase with the Multienzyme Lysosomal Complex of β-Galactosidase, Cathepsin A, and Neuraminidase

Pshezhetsky

Potier

1996

Journal of Biological Chemistry

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“…These arise most commonly from deficiencies in enzymes involved in the degradation or synthesis of carbohydrates. Morquio syndrome is a rare autosomal-recessive mucopolysaccharidosis, first identified in 1929 [162], in which reduced activity of N-acetylgalactosamine-6-sulphate-sulphatase or beta-galactosidase leads to KS and CS-6-sulphate accumulation in connective tissues, including cornea [163]. Several ultrastructural studies on corneas of these patients have revealed membranous inclusions within keratocytes and dense pericellular fibrogranular deposits, plus disrupted lamellae [164][165][166].…”

Section: Ks and Corneal Diseasementioning

confidence: 99%

Structural and biochemical aspects of keratan sulphate in the cornea

Quantock

Young

Akama

2009

Cell. Mol. Life Sci.

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Keratan sulphate (KS) is the predominant glycosaminoglycan (GAG) in the cornea of the eye, where it exists in proteoglycan (PG) form. KS-PGs have long been thought to play a pivotal role in the establishment and maintenance of the array of regularly-spaced and uniformly- thin collagen fibrils which make up the corneal stroma. This characteristic arrangement of fibrils allows light to pass through the cornea. Indeed, perturbations to the synthesis of KS-PG core proteins in genetically altered mice lead to structural matrix alterations and corneal opacification. Similarly, mutations in enzymes responsible for the sulphation of KS-GAG chains are causative for the inherited human disease, macular corneal dystrophy, which is manifested clinically by progressive corneal cloudiness starting in young adulthood.

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“…ARSB specifically cleaves sulfate esters at the 4S position of GalNAc, which are residues in dermatan sulfate and chondroitin sulfate [57][58][59]; SGSH catalyzes the hydrolysis of N-linked sulfamates of glucosamine residues in heparin and heparan sulfate [60]; GALNS is responsible for the hydrolysis of galactose-N6S (GalN6S) residues of keratan sulfate [61,62]; GNS removes the sulfates from glucose-N6S residues in the heparan and keratan sulfate chains [63,64]; and IDS removes the sulfate group from the 2O position of L-iduronic acid in the heparan and dermatan sulfate GAGs [62,65]. In addition, all sulfatases can cleave a variety of synthetic substrates (Table 1).…”

Section: Metabolism and Cell Homeostasis Is Controlled By Lysosomal Smentioning

confidence: 99%

Sulfatase activities towards the regulation of cell metabolism and signaling in mammals

Buono

Cosma

2009

Cell. Mol. Life Sci.

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In higher vertebrates, sulfatases belong to a conserved family of enzymes that are involved in the regulation of cell metabolism and in developmental cell signaling. They cleave the sulfate from sulfate esters contained in hormones, proteins, and complex macromolecules. A highly conserved cysteine in their active site is post-translationally converted into formylglycine by the formylglycine-generating enzyme encoded by SUMF1 (sulfatase modifying factor 1). This post-translational modification activates all sulfatases. Sulfatases are extensively glycosylated proteins and some of them follow trafficking pathways through cells, being secreted and taken up by distant cells. Many proteoglycans, glycoproteins, and glycolipids contain sulfated carbohydrates, which are sulfatase substrates. Indeed, sulfatases operate as decoding factors for a large amount of biological information contained in the structures of the sulfated sugar chains that are covalently linked to proteins and lipids. Modifications to these sulfate groups have pivotal roles in modulating specific signaling pathways and cell metabolism in mammals.

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Morquio's syndrome: Deficiency of a chondroitin sulfate N-acetylhexosamine sulfate sulfatase

Cited by 127 publications

References 5 publications

Association of N-Acetylgalactosamine-6-sulfate Sulfatase with the Multienzyme Lysosomal Complex of β-Galactosidase, Cathepsin A, and Neuraminidase

Association of N-Acetylgalactosamine-6-sulfate Sulfatase with the Multienzyme Lysosomal Complex of β-Galactosidase, Cathepsin A, and Neuraminidase

Structural and biochemical aspects of keratan sulphate in the cornea

Sulfatase activities towards the regulation of cell metabolism and signaling in mammals

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