Tanaka H, Suzuki K
J Neurol Sci. 1978 Oct;38(3):409-19. doi: 10.1016/0022-510x(78)90146-6.
Metabolism of tritium-labelled galactosylceramide and lactosylceramide added to the culture medium was examined in cultured skin fibroblasts from 4 patients with globoid cell leukodystrophy (GLD) and 4 control individuals. The uptake of [3H]galactosylceramide and [3H]lactosylceramide by the fibroblasts continued actively at least up to 3 days. Approximately 30--40% of the galactosylceramide, which had been taken up, was released subsequently from the cells in a 4-day period, whereas only 10% of lactosylceramide was released during the same period. The GLD fibroblasts showed no abnormality in the kinetics of the uptake and in the release of these glycosphingolipids which are natural substrates of the beta-galactosidase genetically deficient in the disorder. This finding differs from that reported for fibroblasts from patients with metachromatic leukodystrophy, which showed abnormal accumulation and retention of sulfatide added to the culture media. However, degradation of added galactosylceramide to [3H]galactose by the GLD fibroblasts was only 25% of the control cells, while lactosylceramide was degraded at 70% of the normal rate. These findings are consistent with the known substrate specificities of the two acidic beta-galactosidases in human tissues; galactosylceramide is hydrolyzed almost exclusively by galactosylceramidase, while lactosylceramide can be hydrolyzed by both galactosylceramidase and GM1-ganglioside beta-galactosidase.
在来自4例球形细胞脑白质营养不良（GLD）患者和4例对照个体的培养皮肤成纤维细胞中，检测了添加到培养基中的氚标记半乳糖神经酰胺和乳糖神经酰胺的代谢情况。成纤维细胞对[3H]半乳糖神经酰胺和[3H]乳糖神经酰胺的摄取至少持续活跃3天。摄取的半乳糖神经酰胺中约30%-40%在4天内随后从细胞中释放出来，而在同一时期只有10%的乳糖神经酰胺被释放。GLD成纤维细胞在摄取动力学以及这些糖鞘脂的释放方面没有异常，这些糖鞘脂是该疾病中基因缺陷的β-半乳糖苷酶的天然底物。这一发现与报道的异染性脑白质营养不良患者的成纤维细胞不同，后者显示添加到培养基中的硫脂有异常积累和滞留。然而，GLD成纤维细胞将添加的半乳糖神经酰胺降解为[3H]半乳糖的量仅为对照细胞的25%，而乳糖神经酰胺的降解率为正常速率的70%。这些发现与人体组织中两种酸性β-半乳糖苷酶已知的底物特异性一致；半乳糖神经酰胺几乎完全由半乳糖神经酰胺酶水解，而乳糖神经酰胺可由半乳糖神经酰胺酶和GM1-神经节苷脂β-半乳糖苷酶两者水解。
