Boer Daphne E C, van Smeden Jeroen, Bouwstra Joke A, Aerts Johannes M F G
Medical Biochemistry, Leiden Institute of Chemistry, Leiden University, Faculty of Science, 2333 CC Leiden, The Netherlands.
Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Faculty of Science, 2333 CC Leiden, The Netherlands.
J Clin Med. 2020 Mar 9;9(3):736. doi: 10.3390/jcm9030736.
Glucocerebrosidase (GCase) is a retaining β-glucosidase with acid pH optimum metabolizing the glycosphingolipid glucosylceramide (GlcCer) to ceramide and glucose. Inherited deficiency of GCase causes the lysosomal storage disorder named Gaucher disease (GD). In GCase-deficient GD patients the accumulation of GlcCer in lysosomes of tissue macrophages is prominent. Based on the above, the key function of GCase as lysosomal hydrolase is well recognized, however it has become apparent that GCase fulfills in the human body at least one other key function beyond lysosomes. Crucially, GCase generates ceramides from GlcCer molecules in the outer part of the skin, a process essential for optimal skin barrier property and survival. This review covers the functions of GCase in and beyond lysosomes and also pays attention to the increasing insight in hitherto unexpected catalytic versatility of the enzyme.
葡萄糖脑苷脂酶（GCase）是一种保留型β-葡萄糖苷酶，最适pH呈酸性，可将糖鞘脂葡萄糖神经酰胺（GlcCer）代谢为神经酰胺和葡萄糖。GCase的遗传性缺乏会导致名为戈谢病（GD）的溶酶体贮积症。在GCase缺乏的GD患者中，组织巨噬细胞溶酶体中GlcCer的积累很显著。基于上述情况，GCase作为溶酶体水解酶的关键功能已得到充分认识，然而，很明显GCase在人体中除了溶酶体之外还至少履行另一项关键功能。至关重要的是，GCase在皮肤外层从GlcCer分子生成神经酰胺，这一过程对于最佳皮肤屏障特性和生存至关重要。本综述涵盖了GCase在溶酶体内外的功能，同时也关注对该酶迄今为止意想不到的催化多功能性的日益深入的认识。
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