Kobayashi T, Shinnoh N, Kuroiwa Y
Biochim Biophys Acta. 1986 Nov 14;879(2):215-20.
The metabolism of galactosylceramide was investigated in normal and twitcher mice, an animal model for human globoid cell leukodystrophy. The findings were compared with data obtained on human tissues. In vitro studies demonstrated that there were two genetically distinct enzymes that hydrolyze galactosylceramide: galactosylceramidase I and II. The former was deficient in the twitcher, while the latter was intact. beta-Galactosidase preparations purified from normal mouse liver possessed the activity to hydrolyze galactosylceramide when the assay conditions for galactosylceramidase II was used. Therefore, galactosylceramidase II was considered to be identical to GM1 ganglioside beta-galactosidase. In contrast to the human enzyme, the murine beta-galactosidase had a relatively high Km value toward galactosylceramide. The galactosylceramide-loading test demonstrated that the twitcher fibroblasts hydrolyzed the lipid at lower rates than seen in cases of human globoid cell leukodystrophy fibroblasts. These differences in galactosylceramidase II between murine and human tissues suggest that galactosylceramide accumulates in twitcher mice but not in humans with globoid cell leukodystrophy, even though galactosylceramidase I is genetically deficient in both human and this mouse model.
在正常小鼠和震颤小鼠（一种人类球状细胞脑白质营养不良的动物模型）中研究了半乳糖神经酰胺的代谢。将研究结果与在人体组织上获得的数据进行了比较。体外研究表明，有两种基因不同的酶可水解半乳糖神经酰胺：半乳糖神经酰胺酶I和II。前者在震颤小鼠中缺乏，而后者是完整的。当使用半乳糖神经酰胺酶II的测定条件时，从正常小鼠肝脏中纯化的β-半乳糖苷酶制剂具有水解半乳糖神经酰胺的活性。因此，半乳糖神经酰胺酶II被认为与GM1神经节苷脂β-半乳糖苷酶相同。与人类酶相比，小鼠β-半乳糖苷酶对半乳糖神经酰胺的Km值相对较高。半乳糖神经酰胺负载试验表明，震颤小鼠成纤维细胞水解脂质的速率低于人类球状细胞脑白质营养不良成纤维细胞。小鼠和人体组织中半乳糖神经酰胺酶II的这些差异表明，即使半乳糖神经酰胺酶I在人类和这种小鼠模型中都存在基因缺陷，但半乳糖神经酰胺在震颤小鼠中积累，而在患有球状细胞脑白质营养不良的人类中则不积累。
