arylsulfatases

Arylsulfatases are a family of enzymes that hydrolyze sulfate esters from a broad range of substrates, including glycosaminoglycans, sulfolipids, and steroid sulfates. They are formylglycine-dependent sulfatases; the catalytic residue is formed post-translationally from a cysteine in the active site by the formylglycine-generating enzyme (FGE). Most arylsulfatases are targeted to lysosomes, where they participate in the degradation of sulfated biomolecules by removing sulfate groups, enabling subsequent breakdown.

Biochemically, arylsulfatases contain a formylglycine (FGly) residue in their active site and require no metal cofactors. FGly acts as a nucleophile to attack the sulfate ester. Many are secretory or lysosomal glycoproteins carrying mannose-6-phosphate tags for lysosomal trafficking.

In humans, several members have well-characterized roles; arylsulfatase A (ARSA) hydrolyzes sulfatides; arylsulfatase B (ARSB) degrades dermatan sulfate and chondroitin-4-sulfate. Deficiency of ARSA causes metachromatic leukodystrophy, a lysosomal storage disorder; ARSB deficiency causes mucopolysaccharidosis type VI (Maroteaux–Lamy syndrome). Other arylsulfatases, such as ARSE and the steroid sulfatase (STS, a related member), participate in cartilage development and steroid metabolism, respectively. Mutations in ARSE can cause X-linked chondrodysplasia punctata.

Clinically, arylsulfatase deficiencies underlie lysosomal storage diseases; disease severity depends on residual activity and substrate accumulated. Treatments include enzyme replacement therapy for some forms (e.g., recombinant ARSB for MPS VI) and supportive care; research continues on gene therapy and alternative strategies.