title: Biochemical discrimination of Hurler and Scheie syndromes.
abstract: 1. Homogenates of cultured skin fibroblasts derived from patients with alpha-L-iduronidase-deficiency disorders (Hurler and Scheie syndromes) were capable of hydrolysing iduronosyl anhydro-[1-3H]mannitol 6-sulphate although at considerably reduced rates compared with normal controls. 2. The Vmax. values of alpha-L-iduronidase from patients with Hurler or Scheie syndromes and from normal controls were 11, 12 and 833 pmol min-1 mg-1 of protein respectively; the corresponding apparent Km values were 656, 50 and 53 mumol/l respectively. The alpha-L-iduronidases from normal and Scheie fibroblast homogenates were shown to exhibit pH optima at 3.6 and 4.1 and were competitively inhibited by both chloride and sulphate ions: Hurler alpha-L-iduronidase activity exhibited the pH optimum at 3.8 and was also inhibited by chloride and to a lesser extent by sulphate ions. 3. The thermal stability of Hurler, Scheie and normal alpha-L-iduronidase activities at 55 degrees C gave half-lives of approximately 1.0, 2.5 and 1.0 h respectively. 4. These biochemical findings clearly demonstrate enzyme differences for these two clinically distinct phenotypes and provide biochemical evidence that the Hurler and Scheie syndromes result from different allelic mutations.
mesh_terms: D002648:Child; D002712:Chlorides / Q000494:pharmacology; D005347:Fibroblasts / Q000201:enzymology; D005937:Glucaric Acid / Q000031:analogs & derivatives; D005966:Glucuronidase / Q000037:antagonists & inhibitors; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007067:Iduronic Acid / Q000031:analogs & derivatives; D007068:Iduronidase / Q000172:deficiency / Q000378:metabolism; D007700:Kinetics; D007783:Lactones / Q000494:pharmacology; D008353:Mannitol / Q000031:analogs & derivatives / Q000378:metabolism; D009083:Mucopolysaccharidoses / Q000201:enzymology*; D008059:Mucopolysaccharidosis I / Q000201:enzymology*; D011506:Proteins; D013431:Sulfates / Q000494:pharmacology
chemical_list: D002712:Chlorides; D007783:Lactones; D011506:Proteins; D013431:Sulfates; D007067:Iduronic Acid; D008353:Mannitol; D005966:Glucuronidase; D007068:Iduronidase; D005937:Glucaric Acid