GM2神经节苷脂贮积症变异型，其中己糖胺酶A的底物特异性发生严重改变。
Variant of GM2-gangliosidosis with hexosaminidase A having a severely changed substrate specificity.
作者信息
Kytzia H J, Hinrichs U, Maire I, Suzuki K, Sandhoff K
出版信息
EMBO J. 1983;2(7):1201-5. doi: 10.1002/j.1460-2075.1983.tb01567.x.
Abstract
The levels of hexosaminidase A activity in cultivated fibroblasts of two patients with GM2-gangliosidosis were close to the normal range with 4-methylumbelliferyl-beta-D-2-acetamido-2-deoxyglucopyranoside and 4-methylumbelliferyl-beta-D-2-acetamido-2-deoxygalactopyranoside as substrates, and the enzymes were normal in most parameters analyzed. However, the enzymes of both patients were almost completely inactive against two specific substrates for hexosaminidase A, rho-nitrophenyl-6-sulfo-2-acetamido-2-deoxy-beta-D-glucopyranoside, and ganglioside GM2 in the presence of GM2-activator. Fibroblast extracts of both patients showed normal hexosaminidase B and GM2-activator activity, the latter was strongly decreased in two cases with variant AB. It is suggested that human hexosaminidase A may contain two different active sites which might be inactivated separately by different mutations.
摘要
以4-甲基伞形酮基-β-D-2-乙酰氨基-2-脱氧葡萄糖苷和4-甲基伞形酮基-β-D-2-乙酰氨基-2-脱氧半乳糖苷为底物时，两名GM2神经节苷脂沉积症患者培养的成纤维细胞中的己糖胺酶A活性水平接近正常范围，且在分析的大多数参数中酶均正常。然而，在GM2激活剂存在的情况下，两名患者的酶对己糖胺酶A的两种特异性底物——对硝基苯基-6-磺基-2-乙酰氨基-2-脱氧-β-D-葡萄糖苷和神经节苷脂GM2几乎完全无活性。两名患者的成纤维细胞提取物显示己糖胺酶B和GM2激活剂活性正常，后者在两例AB变异型病例中显著降低。提示人己糖胺酶A可能含有两个不同的活性位点，它们可能因不同的突变而分别失活。
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