Kooistra T, Lloyd J B
Clin Chim Acta. 1985 Jan 15;145(1):9-16. doi: 10.1016/0009-8981(85)90014-2.
beta-Galactosidase activity but not beta-glucuronidase, N-acetyl-beta-D-galactosaminidase or arylsulphatase A activity, is known to be significantly lower in cultured human skin fibroblasts from patients with cystinosis than in cells from control subjects. Incubation of cell homogenates with disulphide or thiol compounds did not affect beta-galactosidase activity, suggesting that decreased beta-galactosidase activity in affected cells was not caused by the presence of inhibiting substances or absence of activating substances. Incubating cells with 0.5 or 1.0 mmol/l cysteamine, a substance used in the clinical treatment of cystinosis because it depletes cells of excess cystine, greatly decreased beta-galactosidase activity in both cystinotic and normal cells. This effect is shown to result from enzyme instability in lysosomes with raised pH and increased thiol concentration. Thus, cysteamine, although effective in depleting cystinotic cells of excess cystine, may have the undesired side-effect of severely decreasing lysosomal beta-galactosidase.
已知胱氨酸病患者培养的人皮肤成纤维细胞中的β-半乳糖苷酶活性显著低于对照受试者细胞，但β-葡萄糖醛酸酶、N-乙酰-β-D-半乳糖胺酶或芳基硫酸酯酶A活性并非如此。用二硫化合物或硫醇化合物孵育细胞匀浆不会影响β-半乳糖苷酶活性，这表明受影响细胞中β-半乳糖苷酶活性降低并非由抑制物质的存在或激活物质的缺失所致。用0.5或1.0 mmol/L半胱胺（一种用于胱氨酸病临床治疗的物质，因为它能使细胞中的过量胱氨酸耗尽）孵育细胞，会使胱氨酸病患者细胞和正常细胞中的β-半乳糖苷酶活性大幅降低。这种效应被证明是由于溶酶体中pH升高和硫醇浓度增加导致酶不稳定所致。因此，半胱胺虽然能有效耗尽胱氨酸病患者细胞中的过量胱氨酸，但可能会产生严重降低溶酶体β-半乳糖苷酶活性的不良副作用。
