SULFATASES, LYSOSOMES AND DISEASE

The properties of several purified sulfatases and the deficiency diseases associated with them were discussed. Mammalian sulfatase isolated from ox liver, human urine and liver is an acidic glycoprotein with a high proline content and a MW of .apprx. 100,000 at pH 7, which reversibly self-associates at lower pH values and which is made up of 2 similar subunits of MW .apprx. 50,000. Sulfatase can hydrolyse nitrocatechol sulfate, aryl sulfate and ascorbic acid 2-sulfate. The most powerful known inhibitor of sulfatase A is SO32-, a competitive inhibitor. Sulfatase A also has cerebroside sulfatase activity in the presence of a bile salt and Mn2+ and is capable of hydrolysing other lipids containing galactosyl 3-phosphate residues: seminolipid, psychosine sulfate and lactosyl sulfate. During hydrolysis of nitrocatechol sulfate sulfatase A is converted into an inactive form which can be reconverted by SO42- and by some other anions. The sulfatase B of ox liver has been obtained as a homogeneous protein but, unlike sulfatase A, exists in a number of closely related forms (BIx, BiB). It is a glycoprotein with a high proline content and contains high amounts of lysine and arginine. The MW for the 2 fractions was 47,000. Sulfatase B has shown arylsulfatase, N-acetylgalactosamine 4-sulfatase and cerebroside activity. Sulfatase C has been identified as a microsomal arglsulfatase. It also shows steroid sulfatase activity. A number of rare metabolic diseases are associated with sulfatase defects. Metachromatic leucodystrophy, or sulfatide lipidosis, is characterized by degeneration of the myelin associated with an accumulation of cerebroside sulfate due to a deficiency of sulfatase A. Maroteaux-Lamy syndrome (Mucopolysaccharidosis VI) results in the accumulation and excretion of large amounts of mucopolysaccharides, mainly dermatan sulfate, and is due to a deficiency of sulfatase B. Hunter syndrome (Mucopolysaccharidosis II) is characterized by a degradation of dermation and heparan sulfate and deficient of a sulfoiduronate sulfatase activity. SanFilippo A syndrome (Mucopolysaccharidosis III) exhibits an excretion of heparin sulfate and a heparin sulfate N-sulfatase activity is lacking: Morquio''s syndrome (Mucopolysaccharidosis IV) is a defect in the degradation of Keraton and chondroitin sulfates and the fibroblast are deficient in a N-acetyl-galactosamine G-sulfatase activity. Multiple sulfatase deficiency is the result of arylsulfatase and steroid inactivity which causes a buildup of cerebroside sulfate, steroid sulfates and polysaccharide sulfates. Placental sulfatase deficiency causes a reduced estrogen excretion during pregnancy which was associated with a placental steroid sulfatase deficiency.