Lysosomal enzymes sphingolipid degradation

The polar lipids of membranes undergo constant metabolic turnover, the rate of their synthesis normally counterbalanced by the rate of breakdown. The breakdown of lipids is promoted by hydrolytic enzymes in lysosomes, each enzyme capable of hydrolyzing a specific bond. When sphingolipid degradation is impaired by a defect in one of these enzymes (Fig. 1), partial breakdown products accumulate in the tissues, causing serious disease. 

A deficiency of lysosomal enzymes results in the inability to degrade the carbohydrate portions of proteoglycans or sphingolipids. Partially digested products accumulate in lysosomes. Tissues become engorged with these residual bodies, and their function is impaired. These diseases are often fatal. 

During degradation, the phosphocholine and sugar units of the sphingolipids are removed by lysosomal enzymes. 

Sphingolipids are degraded by lysosomal enzymes (see Chapter 30). Deficiencies of these enzymes result in a group of lysosomal storage diseases known as the sphingolipidoses. 

Tay-sachs disease A genetic disease caused by a deficiency of the lysosomal enzyme N-acetylhexosaminidase A, which is involved in sphingolipid degradation. The... 

Not only the deficiency of a hydrolytic enzyme, but also of other proteins required for sphingolipid degradation can cause a sphingolipid storage disease. Besides deficiencies of activator proteins, this is the case in galactosialidosis. This disease is characterized by the secondary deficiency of P-galactosidase and sialidase activity. The primary defect is due to mutations within the protective protein, which forms a stable complex with the GMl-p-galactosidase and the lysosomal sialidase [47]. 

Sphingolipids released when membrane is degraded are digested in endosomes after fusion with lysosomes. Lysosomes contain many enzymes, each of which removes specific groups from individual sphingolipids. Genetic deficiencies of many of these enzymes are known, and the diseases share some of the characteristics of I-cell disease discussed in Chapter 4. Table 1-16-1 summarizes these. 

Each lysosomal storage disease (see p. 49) is caused by a hereditary deficiency of an enzyme required for the degradation of a specific metabolite. Several lysosomal storage diseases are associated with sphingolipid metabolism. Most of... 

The synthesis of all sphingolipids begins with the production of ceramide. Sphingolipids are degraded within lysosomes by specific hydrolytic enzymes. 

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