The disorder of hyaluronic acid metabolism in cultured skin fibroblasts derived from a patient with the Hurler syndrome.
The metabolism of hyaluronic acid in cultured skin fibroblasts derived from a patient with the Hurler syndrome and from a normal subject was examined. 1. An increased net incorporation of [(3)H]glucose into the hyaluronic acid fraction of the Hurler-syndrome cells occurred when compared with normal cells. 2. During a ;chase' period, approx. 35% of the radioactivity derived from glucose was lost from the hyaluronic acid fraction of the Hurler-syndrome cells, whereas the normal cells retained all their radioactivity. 3. Although the Hurler-syndrome cells contained a ninefold greater amount of hyaluronic acid than normal cells, simultaneous determination of the specific radioactivity derived from the label revealed a value for the Hurler-syndrome cells one-half that of normal cells. These results are taken to indicate that the Hurler cells synthesize hyaluronic acid de novo at a higher rate than do normal cells. 4. Exposure of Hurler-syndrome cultured fibroblasts to a crude urine corrective-factor preparation (Neufeld & Cantz, 1971), now known to contain alpha-l-iduronidase, the specific Hurler-syndrome corrective factor (Bach et al., 1972), decreased the hyaluronic acid content to near-normal values before any effect was observed on [(3)H]glucose incorporation into the hyaluronic acid fraction. 5. In addition, the hyaluronic acid content of the normal cells decreased after exposure to the corrective factor of urine. 6. The mobilization of hyaluronic acid in Hurler-syndrome and normal cells exposed to the crude corrective-factor preparation of urine caused a decrease in specific radioactivity in the ;corrected' Hurler-syndrome cells and an increase in specific radioactivity in the ;corrected' normal cells.
D001692:Biological Transport; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000652:urine; D006601:Hexoses; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis / Q000378:metabolism*; D007553:Isotope Labeling; D007700:Kinetics; D008059:Mucopolysaccharidosis I / Q000235:genetics* / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium; D014574:Uronic Acids
D006601:Hexoses; D014574:Uronic Acids; D014316:Tritium; D006820:Hyaluronic Acid; D006026:Glycoside Hydrolases; D005947:Glucose