Defects in degradation of blood group A and B glycosphingolipids in Schindler and Fabry diseases the nomenclature used for neutral glycolipids follows the IUPAC-IUB recommendation (1). DOI 10.1194/jlr.M100423-JLR200
Defects in degradation of blood group A and B glycosphingolipids in Schindler and Fabry diseases the nomenclature used for neutral glycolipids follows the IUPAC-IUB recommendation (1). DOI 10.1194/jlr.M100423-JLR200
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Schindler 和 Fabry 疾病中 A 型和 B 型血型鞘糖脂降解缺陷中性糖脂的命名遵循 IUPAC-IUB 推荐 (1)。
DOI：
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发表时间：
2002
影响因子：
6.5
通讯作者：
D. Schindler
中科院分区：
文献类型：
--
作者：
B. Asfaw;J. Ledvinová;R. Dobrovolný;H. Bakker;R. Desnick;O. V. van Diggelen;J. de Jong;T. Kanzaki;A. Chabás;I. Maire;E. Conzelmann;D. Schindler
采用遗传性溶酶体酶病、α- n -乙酰半乳糖苷酶（α-NAGA）和α-半乳糖苷酶A缺乏症（分别为Schindler病和Fabry病）患者和正常对照组皮肤成纤维细胞培养物，研究了A型和B型鞘糖脂的原位降解。糖鞘脂A-6-2 (GalNAc(α1→3)[fucα α1→2]Gal(β1→4)GlcNAc(β1→3)Gal（β1→4)Glc（β1→1′）Cer， IV2-α- focusyl-IV3-α- n -乙酰半乳糖氨基基新乳酸四聚神经酰胺），B-6-2 (Gal(α1→3)[fucα α1→2]Gal(β1→3)Gal（β1→4)Glc（β1→1′）Cer， IV2-α- focusyl-IV3-α-半乳糖基新乳酸四聚神经酰胺），globo苷(GalNAc(β1→3)Gal(α1→4)Gal(β1→4)Gal(β1→4)Gal(β1→4)Gal(β1→4)Glc（β1→1′）Cer， globo苷(GalNAc(β1→3)Gal(α1→4)Gal（β1→4)Glc（β1→1′）Cer， globo四聚神经酰胺）在其神经酰胺部分进行氚标记，作为天然底物使用。在所有α- naga缺陷患者的成纤维细胞中，糖脂A-6-2的降解率非常低（低于对照组的7%），尽管临床表现非常不同，排除了不同的残留酶活性作为临床异质性的解释。在一名A型血患者中检测到尿中A型血的糖脂分泌量明显升高（比对照组的上限高5倍），这支持了A型血的活性糖脂可能作为储存化合物在A型血患者中起作用的观点。当糖脂B-6-2被喂给α-半乳糖苷酶a缺乏的细胞时，其降解率惊人地高（为对照组的50%），而globotriaosylneuroide的降解率降至对照组平均水平的15%以下，这可能反映了极性糖脂与非极性糖脂在溶酶体酶学上的差异。α-d-半乳糖基部分对底物的相对高度降解暗示可能有其他酶的作用。
Skin fibroblast cultures from patients with inherited lysosomal enzymopathies, α-N-acetylgalactosaminidase (α-NAGA) and α-galactosidase A deficiencies (Schindler and Fabry disease, respectively), and from normal controls were used to study in situ degradation of blood group A and B glycosphingolipids. Glycosphingolipids A-6-2 (GalNAc (α1→3)[Fucα1→2]Gal(β1→4)GlcNAc(β1→3)Gal(β1→ 4)Glc (β1→1′)Cer, IV2-α-fucosyl-IV3-α-N-acetylgalactosaminylneolactotetraosylceramide), B-6-2 (Gal(α1→3)[Fucα1→ 2] Gal (β1→4)GlcNAc(β1→3)Gal(β1→4)Glc(β1→1′)Cer, IV2- α-fucosyl-IV3-α-galactosylneolactotetraosylceramide), and globoside (GalNAc(β1→3)Gal(α1→4)Gal(β1→4)Glc(β1→1′) Cer, globotetraosylceramide) were tritium labeled in their ceramide moiety and used as natural substrates. The degradation rate of glycolipid A-6-2 was very low in fibroblasts of all the α-NAGA-deficient patients (less than 7% of controls), despite very heterogeneous clinical pictures, ruling out different residual enzyme activities as an explanation for the clinical heterogeneity. Strongly elevated urinary excretion of blood group A glycolipids was detected in one patient with blood group A, secretor status (five times higher than upper limit of controls), in support of the notion that blood group A-active glycolipids may contribute as storage compounds in blood group A patients. When glycolipid B-6-2 was fed to α-galactosidase A-deficient cells, the degradation rate was surprisingly high (50% of controls), while that of globotriaosylceramide was reduced to less than 15% of control average, presumably reflecting differences in the lysosomal enzymology of polar glycolipids versus less-polar ones. Relatively high-degree degradation of substrates with α-d-Galactosyl moieties hints at a possible contribution of other enzymes.
溶酶体α-N-乙酰半乳糖胺酶缺乏症，弥漫性体质血管角化瘤伴糖肽尿的酶缺陷。
DOI：
10.1172/jci115357
发表时间：
1991
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Kanzaki,T;Wang,AM;Desnick,RJ
通讯作者：
Desnick,RJ
人 α-N-乙酰氨基半乳糖苷酶分子克隆、核苷酸序列和全长 cDNA 的表达。
DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Wang,AM;Bishop,DF;Desnick,RJ
通讯作者：
Desnick,RJ