Kolter Thomas, Sandhoff Konrad
Kekulé-Institut für Organische Chemie und Biochemie der Universität, 53121 Bonn, Germany.
Annu Rev Cell Dev Biol. 2005;21:81-103. doi: 10.1146/annurev.cellbio.21.122303.120013.
Sphingolipids and glycosphingolipids are membrane components of eukaryotic cell surfaces. Their constitutive degradation takes place on the surface of intra-endosomal and intra-lysosomal membrane structures. During endocytosis, these intra-lysosomal membranes are formed and prepared for digestion by a lipid-sorting process during which their cholesterol content decreases and the concentration of the negatively charged bis(monoacylglycero)phosphate (BMP)--erroneously also called lysobisphosphatidic acid (LBPA)--increases. Glycosphingolipid degradation requires the presence of water-soluble acid exohydrolases, sphingolipid activator proteins, and anionic phospholipids like BMP. The lysosomal degradation of sphingolipids with short hydrophilic head groups requires the presence of sphingolipid activator proteins (SAPs). These are the saposins (Saps) and the GM2 activator protein. Sphingolipid activator proteins are membrane-perturbing and lipid-binding proteins with different specificities for the bound lipid and the activated enzyme-catalyzed reaction. Their inherited deficiency leads to sphingolipid- and membrane-storage diseases. Sphingolipid activator proteins not only facilitate glycolipid digestion but also act as glycolipid transfer proteins facilitating the association of lipid antigens with immunoreceptors of the CD1 family.
鞘脂类和糖鞘脂类是真核细胞表面的膜成分。它们的组成性降解发生在内体和溶酶体内膜结构的表面。在胞吞作用过程中，这些溶酶体内膜形成并通过脂质分选过程为消化做准备，在此过程中其胆固醇含量降低，而带负电荷的双（单酰甘油）磷酸酯（BMP）——也被错误地称为溶血双磷脂酸（LBPA）——的浓度增加。糖鞘脂类的降解需要水溶性酸性外切水解酶、鞘脂激活蛋白以及像BMP这样的阴离子磷脂的存在。具有短亲水头基团的鞘脂类的溶酶体降解需要鞘脂激活蛋白（SAPs）的存在。这些蛋白包括鞘脂激活蛋白原（Saps）和GM2激活蛋白。鞘脂激活蛋白是具有膜扰动性和脂质结合性的蛋白质，对结合的脂质和激活的酶催化反应具有不同的特异性。它们的遗传性缺乏会导致鞘脂类和膜储存疾病。鞘脂激活蛋白不仅促进糖脂消化，还作为糖脂转移蛋白促进脂质抗原与CD1家族免疫受体的结合。
