Sphingomyelinase of Human Tissues

Abstract

Sphingomyelinase (sphingomyelin phosphodiesterase, E.C. 3.1.4. 12) catalyzes hydrolysis of sphingomyelin to ceramide and phosphorylcholine. A genetic deficiency of this enzyme characterizes at least two distinct clinical forms of Niemann-Pick disease (Crocker’s Type A and Type B (1)). Patients with the Type A disease exhibit severe neurological manifestations, while patients with the Type B disease are completely intact neurologically. The systemic accumulations of sphingomyelin are similar in the two types. The degree of the sphingomyelinase deficiency in the liver, spleen, leukocytes, or fibroblasts is similar in both of the clinical types and does not appear to explain the dramatic phenotypic difference (2). An alternative possibility would be that sphingomyelinase might be organ-specific in itself or in the distribution of isozymes and that different mutations can cause differential inactivation of the enzyme in different organs. In addition to the above sphingomyelinase with the acidic pH optimum, there is another enzyme which also hydrolyzes sphingomyelin but at neutral pH in the presence of magnesium ions (3–5). The relationship, if any, of this magnesium-dependent neutral sphingomyelinase to either the acidic sphingomyelinase or NiemannPick disease is not clear at the present time.