Sphingomyelinase enzymes

Sphingomyelin, a ubiquitous component of cell membranes, especially neuronal membranes, is normally degraded within lysosomes by the enzyme sphingomyelinase. 

For example, Niemann-Piclc disease is caused by a rare genetic defect in the enzyme sphingomyelinase, which cleaves phosphocholine from sphingomyelin. Sphingomyelin accumulates in the brain, spleen, and liver. The disease becomes evident in infants, and causes mental retardation and early death. More common is Tay-Sachs disease, in which ganglioside GM2 accumulates in the brain and spleen (Fig. 2) owing to lack of the enzyme hexosaminidase A. The symptoms of Tay-Sachs disease are progressive retardation in development, paralysis, blindness, and death by the age of 3 or 4 years. 

Of the four subtypes of Niemann-Pick disease, type A is the most severe. It is inherited as a recessive disorder (i.e., a defective copy of the gene must be inherited from each parent) that results in an absence of the enzyme sphingomyelinase. The absence of this enzyme causes the storage of large amounts of sphingomyelin and cholesterol in the brain, bone marrow, liver, and spleen. 

Partial answers to the pathogenesis of Niemann-Pick disease have been obtained recently. An enzyme, sphingomyelinase, which hydrolyzes sphingomyelin to yield phosphorylcholine and ceramide has been found and partially purified from liver. Drastic reduction in the activity of this enzyme has been found in at least some patients with Niemann-Pick disease (see Fig. 3-40). In other cases the biochemical defect remains unknown [125], especially in those forms of the disease in which cholesterol accumulates (Nova Scotia variant). 

A lipidosis characterized by the presence of increased amounts of sphingomyelin in the tissues. Four types (A-D) have been recognized. In types A and B, a deficiency of the lysozomal enzyme, sphingomyelinase, has been demonstrated. Type A affects the nervous system and carries a poor prognosis. Splenomegaly is the main feature of type B and affected individuals may survive to adulthood. 

These are lipids containing a fatty acid, phosphoric acid, choline and the amino alcohol, sphingosine. They are deposited in the tissues in Niemann-Pick disease, a disorder of lipid storage. In some forms of this disease, a deficiency of the lysosomal enzyme, sphingomyelinase, can be demonstrated. 

Niemann-Piek disaase Isphingomyelin lipidesis) (Also see FATS AND OTHER LIPIOS.I taifficiBizt levels of the enzyme sphingomyelinase. Accumulation chiefly ol sphingomyelin and lecithin in the livei. spleen, and central nervous system, enlarged liver and sple mental and physical retardation cherry red spot on retina of eye. None of value. 

The two most likely candidates are amylopectin and glycogen. Glycogen is more highly branched and therefore has more nonreducing end residues. Look for the substance that has no NeuNAc. The only one is cerebroside. Niemann-Pick disease is caused by a deficiency in sphingomyelinase. It has been used to treat this disease. The treatment is termed enzyme replacement therapy. 

Acid sphingomyelinase is a lysosomal enzyme that catalyzes the breakdown of sphingomyelin to ceramide and phosphoryl-choline.A deficiency of this enzyme leads to lysosomal accumulation of sphingomyelin in patients with Niemann-Pick disease. Recent data indicate that correct intracellular targeting of acid sphingomyelinase to lysosomes is dependent on the mannose 6-phosphate-mediated pathway. Does this imply that the I-cell patient will present with Niemann-Pick symptoms Can I-cell disease be viewed as a constellation of many lysosomal storage diseases ... 

---