Lysosomal glycosphingolipid catabolism by acid ceramidase: formation of glycosphingoid bases during deficiency of glycosidases
Lysosomal glycosphingolipid catabolism by acid ceramidase: formation of glycosphingoid bases during deficiency of glycosidases
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DOI：
10.1002/1873-3468.12104
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发表时间：
2016-03-01
期刊：
影响因子：
3.5
通讯作者：
Aerts, Johannes M.
中科院分区：
文献类型：
--
作者：
Ferraz, Maria J.;Marques, Andre R. A.;Aerts, Johannes M.
遗传性溶酶体贮积性疾病伴鞘糖脂分解代谢糖苷酶活性不足时，鞘糖基升高。我们研究了葡萄糖脑苷酶缺乏症（戈谢病）和α -半乳糖苷酶A缺乏症（法布里病）中葡萄糖脑苷和globotriaosylsphingosin形成的分子基础。独立的遗传和药理学证据表明，酸性神经酰胺酶通过溶酶体鞘糖脂的去酰化在这两个过程中发挥积极作用。讨论了溶酶体糖苷酶缺陷患者通过这种替代代谢产生的糖鞘碱升高的潜在病理生理相关性。
Glycosphingoid bases are elevated in inherited lysosomal storage disorders with deficient activity of glycosphingolipid catabolizing glycosidases. We investigated the molecular basis of the formation of glucosylsphingosine and globotriaosylsphingosine during deficiency of glucocerebrosidase (Gaucher disease) and alpha-galactosidase A (Fabry disease). Independent genetic and pharmacological evidence is presented pointing to an active role of acid ceramidase in both processes through deacylation of lysosomal glycosphingolipids. The potential pathophysiological relevance of elevated glycosphingoid bases generated through this alternative metabolism in patients suffering from lysosomal glycosidase defects is discussed.