| Autor: |
van Diggelen OP; Department of Clinical Genetics, Erasmus University Medical Centre, Rotterdam, The Netherlands. o.vandiggelen@erasmusmc.nl, Voznyi YV, Keulemans JL, Schoonderwoerd K, Ledvinova J, Mengel E, Zschiesche M, Santer R, Harzer K |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of inherited metabolic disease [J Inherit Metab Dis] 2005; Vol. 28 (5), pp. 733-41. |
| DOI: |
10.1007/s10545-005-0105-y |
| Abstrakt: |
6-Hexadecanoylamino-4-methylumbelliferylphosphorylcholine (HMUPC) was shown to be a specific substrate for the determination of acid (lysosomal) sphingomyelinase (ASM; gene SMPD1). Fibroblasts (n = 27) and leukocytes (n = 8) from both the A and B types of Niemann-Pick disease showed < 6% and < 10% of mean normal ASM activity, respectively. Niemann-Pick A or B patients bearing the Q292K mutation had apparently normal ASM activity with our new artificial substrate. These patients with false-normal sphingomyelinase activity, however, could readily be detected by determining the extent of inhibition of enzymatic hydrolysis of the artificial substrate HMU-PC by an unlabelled natural substrate, in particular lysosphingomyelin. This approach is generally applicable. Our novel assay for ASM combines the ease of a rapid and robust enzyme assay using a fluorogenic substrate with the specificity of an ASM assay using a natural substrate. Such assays are obviously more convenient to the diagnostic laboratory, since radiolabelled substrates are not required. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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