deoxycholic-acid and Leukodystrophy--Metachromatic

The cholate and taurodeoxycholate activations of cerebroside sulphate sulphohydrolase (cerebroside-3-sulphate 3-sulphohydrolase, EC 3.1.6.8) activity of arylsulphatase A (aryl-sulphate sulphohydrolase, EC 3.1.6.1) were compared. Taurodeoxycholate caused a sharp peak of response at a concentration of 1.25 mg/ml (type-I activation). Cholate also showed type-I activation but, in addition, it evoked a second, higher, response plateau at concentrations between 5 and 10 mg/ml (type-II activation). At the pH of the reaction, cholate is converted largely to the sparingly soluble free aicd, so at the high concentrations associated with type-II activation, copious precipitates were formed. It was found that the precipitated material was essential for the type-II activation. Type-I activation appears to involve bile salt interaction with substrate, while type-II activation appears to involve enzyme interaction with solid-phase cholic acid. the putative mutant arylsulphatase A in an unusual form of metachromatic leukodystrophy hydolysed cerebroside sulphate only in the presence of high levels of cholate. The type-II activation may thus be simulating a physiological desulphation reaction.

Topics: Cerebroside-Sulfatase; Cerebrosides; Chemical Precipitation; Cholic Acids; Deoxycholic Acid; Enzyme Activation; Fibroblasts; Humans; Leukodystrophy, Metachromatic; Sulfatases; Taurodeoxycholic Acid

Topics: Barium; Cells, Cultured; Cholic Acids; Chromatography, Thin Layer; Copper; Deoxycholic Acid; Drug Stability; Fibroblasts; Galactose; Humans; Hydrogen-Ion Concentration; Isoelectric Focusing; Kinetics; Leukodystrophy, Metachromatic; Manganese; Mercury; Skin; Sphingosine; Sulfatases; Sulfur Radioisotopes; Surface-Active Agents; Taurocholic Acid; Temperature; Time Factors; Zinc