Lysosomes glycosphingolipid catabolism

Catabolism of some glycosphingolipids. The glycosyl hydrolase enzymes involved in these reactions are localized in the lysosomes. 

However, castanospermine also inhibits the activity of lysosomal p-glucosidase and this affects the catabolism of glycosphingolipids. ... 

Synthesis of glycosphingolipids and sulfoglycosphin-golipids involves the addition of sugar and sulfate residues to ceramide from UDP-sugar derivatives or the activated sulfate donor 3 -phosphoadenosine-5 -phosphosulfate (Chapter 17), and appropriate transferases. These pathways are discussed in Chapter 16. Catabolism of sphingolipids is by specific lysosomal hydrolases. Several inherited disorders associated with the deficiencies of these enzymes are discussed below. 

Glycosphingolipids are catabolized by the stepwise hydrolysis of the terminal monosaccharides through the concerted action of a series of specific exoglycosidases (Fig. 10) [12]. There is often a requirement for SAPs, SAP-A, -B, -C, or -D, and GM2-activator protein, which is required for GM2 hydrolysis but can also accommodate other glycosphingolipids. Acidic lipids, and in particular BMP, are additionally involved in vivo as stimulators of glycosidase activity and are components of the lysosomal perimeter membrane. 

The enzymes involved in the metabolism of glycosphingolipids are particle bound. Biological synthesis and degradation is catalyzed by two enzyme systems, perhaps multienzyme complexes, which differ in localization and pH optima. Enzymes of anabolism are found mainly in microsomal fractions and show highest activity at about pH 7 catabolic enzymes predominate in preparations rich in lysosomes and have optima of activity about pH 5. 

---