Arylsulfatase B

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Arylsulfatase B (N-acetylgalactosamine-4-sulfatase, chondroitinsulfatase, chondroitinase, acetylgalactosamine 4-sulfatase, N-acetylgalactosamine 4-sulfate sulfohydrolase,

Arylsulfatase B is among a group of arylsulfatase enzymes present in the lysosomes of the liver, pancreas, and kidneys of animals. The purpose of the enzyme is to hydrolyze sulfates in the body. ARSB does this by breaking down glycosaminoglycans (GAGs), which are large sugar molecules in the body. ARSB targets two GAGs in particular: dermatan sulfate and chondroitin sulfate.^[7]

Over 130 mutations to ARSB have been found, each leading to a deficiency in the body. In most cases, the mutation occurs on a single nucleotide in the sequence. An arylsulfatase B deficiency can lead to an accumulation of GAGs in lysosomes,^[7] which in turn can lead to mucopolysaccharidosis VI.

Used as a pharmaceutical drug, the enzyme is known under the

Structure

The primary structure of Escherichia coli arylsulfatase B contains a primary sequence of 502 amino acids. Its secondary structure is quite complex, containing numerous alpha helices (20 total containing 138 residues) and beta sheets (21 strands total containing 87 residues).^[5] The functional enzyme is believed to be a homo tetramer. Due to the complexity of arylsulfatase B's secondary structure, many hydrophobic and hydrophilic regions are present, as demonstrated by the Kyte-Doolittle hydropathy plot:

Medical uses

Galsulfase is used to treat adults and children who have mucopolysaccharidosis VI (MPS VI or Maroteaux-Lamy syndrome).^[10] This disease is caused by the lack of an enzyme called N-acetylgalactosamine 4-sulfatase, which is needed to break down substances in the body called glycosaminoglycans (GAGs).^[10] If the enzyme is not present, GAGs cannot be broken down and they build up in the cells.^[10] This causes the signs of the disease, the most noticeable being a short body, a large head and difficulty moving about.^[10] The disease is usually diagnosed in infants between one and five years of age.^[10] Galsulfase has been shown to improve walking and stair-climbing capacity.^[12]

The most common adverse reactions (≥10%) are: rash, pain, urticaria, pyrexia, pruritus, chills, headache, nausea, vomiting, abdominal pain and dyspnea.^[12] The most common adverse reactions requiring interventions are infusion-related reactions.^[12]

Galsulfase (N-acetylgalactosamine-4-sulfatase, recombinant human) was granted orphan drug designation by both the European Commission and the U.S. Food and Drug Administration (FDA).^[13][14]

Role in cystic fibrosis

Expression and activity of ARSB were found to be related to the function of cystic fibrosis transmembrane conductance regulator (CFTR), the membrane channel deficient in cystic fibrosis. Measurements in cystic fibrosis cell line IB3 and its derivative cell line C38, which has a functional CFTR, showed increased ARSB activity and expression in the C38 line.^[15] CFTR potentiator VRT-532 increased ARSB expression and activity in cystic fibrosis cells to the level in the normal bronchial epithelial cells.^[16]

Role in malignancy

ARSB has been studied in a variety of cancers. Cultured normal mammary epithelial and

• Aryl
• Sulfatase

References