Tallman J F, Johnson W G, Brady R O
J Clin Invest. 1972 Sep;51(9):2339-45. doi: 10.1172/JCI107045.
The catabolism of Tay-Sachs ganglioside, N-acetylgalactosaminyl- (N-acetylneuraminosyl) -galactosylglucosylceramide, has been studied in lysosomal preparations from normal human brain and brain obtained at biopsy from Tay-Sachs patients. Utilizing Tay-Sachs ganglioside labeled with (14)C in the N-acetylgalactosaminyl portion or (3)H in the N-acetylneuraminosyl portion, the catabolism of Tay-Sachs ganglioside may be initiated by either the removal of the molecule of N-acetylgalactosamine or N-acetylneuraminic acid. The activity of the N-acetylgalactosamine-cleaving enzyme (hexosaminidase) is drastically diminished in such preparations from Tay-Sachs brain whereas the activity of the N-acetylneuraminic acid-cleaving enzyme (neuraminidase) is at a normal level. Total hexosaminidase activity as measured with an artificial fluorogenic substrate is increased in tissues obtained from patients with the B variant form of Tay-Sachs disease and it is virtually absent in the O-variant patients. The addition of purified neuraminidase and various purified hexosaminidases exerted only a minimal synergistic effect on the hydrolysis of Tay-Sachs ganglioside in the lysosomal preparations from the control or patient with the O variant of Tay-Sachs disease.
已对来自正常人类大脑以及取自泰-萨克斯病患者活检大脑的溶酶体制剂中泰-萨克斯神经节苷脂（N-乙酰半乳糖胺基-（N-乙酰神经氨酸基）-半乳糖基葡糖神经酰胺）的分解代谢进行了研究。利用在N-乙酰半乳糖胺部分用（14）C标记或在N-乙酰神经氨酸部分用（3）H标记的泰-萨克斯神经节苷脂，泰-萨克斯神经节苷脂的分解代谢可通过去除N-乙酰半乳糖胺分子或N-乙酰神经氨酸分子来启动。在取自泰-萨克斯病大脑的此类制剂中，N-乙酰半乳糖胺裂解酶（己糖胺酶）的活性急剧降低，而N-乙酰神经氨酸裂解酶（神经氨酸酶）的活性处于正常水平。用人工荧光底物测定的总己糖胺酶活性在患有B型变异型泰-萨克斯病的患者所获得的组织中增加，而在O型变异型患者中实际上不存在。添加纯化的神经氨酸酶和各种纯化的己糖胺酶对来自对照或O型变异型泰-萨克斯病患者的溶酶体制剂中泰-萨克斯神经节苷脂的水解仅产生最小的协同作用。
