Activator Proteins (Protein Cofactors) for the Catabolism of Glycosphingolipids
Through the work of several laboratories in the past fifteen years, it has been established that the catabolism of several glycosphingolipids requires protein cofactors called protein activators or activator proteins (1–3). The discovery of activator proteins represents one of the most exciting developments in the field of glycosphingolipid catabolism. While the discovery of activator proteins introduced a new concept to the catabolism of glycosphingolipids, we know very little about the specificities and mechanism of actions of these intriguing proteins. Since our initial reports of the activator proteins for the enzymatic hydrolysis of GM2 in 1973 (4) and that for the hydrolysis of GM1 in 1976 (5), we have been studying the specificities of these two activator proteins. We found that these two activator proteins differ greatly in their specificities. The activator protein isolated by monitoring the enzymatic hydrolysis of GM1 (5) was found to stimulate the hydrolyses of a wide variety of glycolipids catalyzed by glycosidases isolated from various sources. The function of this activator protein can be regarded as that of a detergent which assists the dispersion of lipid substrates. We, therefore, propose to name this activator protein “DISPERSIN.” The activator protein which was isolated by following the hydrolysis of GM2 (4,6,7) was found to be highly specific for the hydrolysis of GalNAc from GM2 and the glycosphingolipids with the terminal structure similar to that of GM2, such as GalNAc-GM1b. This activator protein can also stimulate the hydrolysis of GalNAc from monosulfo-GgOse 3Cer (SM2). Structurally, SM2 has a close resemblance to GM2; in SM2 the acidic group is a sulfate instead of a NeuAc. Therefore, it is still convenient to call this activator protein “GM2-Activator.” This chapter briefly describes our work on activator proteins essential for the catabolism of glycosphingolipids.
KeywordsEnzymatic Hydrolysis Sialic Acid Activator Protein Human Spleen Sodium Taurodeoxycholate
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