Sphingomyelinases and Niemann-Pick disease

Abstract

In the first part the properties of normal mammalian sphingomyelinases are reviewed: The lysosomal acid sphingomyelinase is a polymeric glycoprotein (subunit Mr between 28 000 and 70 000) which hydrolyses natural sphingomyelin, coloured and fluorescent semi-synthetic analogues (trinitrophenyl-aminolauryl-sphingomyelin and pyrenedecanoyl-sphingomyelin) and the synthetic analogue 2-N-hexadecanoylamido-nitrophenyl-phosphorylcholine. The suitability of these substrates and of synthetic fluorescent derivatives of methylumbelliferone is discussed. The effect of lipids, detergents and other effectors on the enzyme activity is also described. The neutral sphingomyelinase from brain tissue, localized in cell membranes, has a high Mr (160 000 and 600 000), is heat labile, hydrolyses sphingomyelin and its coloured and fluorescent analogues, but not 2-N-hexadecanoylamido-nitrophenyl-phosphorylcholine. A new method is available for determining enzyme activity in the intact cell through the utilization of endogenous or exogenous sphingomyelin as substrate. In the second part of the review, the classification of Niemann-Pick disease, the characteristic features of each type and the biological tools used for the diagnosis are reported. Experimental models (animal models and cellular models in culture) are reviewed with a particular attention to a new model system, Epstein-Barr virus-transformed lymphoid cell lines.