The metabolism of sphingomyelin. II. Evidence of an enzymatic deficiency in Niemann-Pick diseae.

Abstract

The accumulation of excessive quantities of sphingomyelin in tissues of patients with Niemann-Pick disease was demonstrated by Klenk in 19341, 2 and has been amply confirmed by other investigators.3-5A study by Crocker and Mays6 in- dicated that the rate of biosynthesis of sphingomyelin in tissues from these patients appeared to be essentially normal.These findings suggested that the metabolic lesion in this condition might be of a catabolic nature.We have recently obtained evidence for the presence of a specific enzyme in liver tissue which catalyzes the hydrolysis of sphingomyelin.7 The enzyme was partially purified from rat liver tissue, and the products of the reaction were demonstrated to be phosphorylcholine and ceramide.The most highly purified enzyme preparations did not catalyze the hydrolysis of lecithin or phosphatidylethanolamine.Lecithin, however, appeared to be a competitive inhibitor of the reaction.Similar enzymatic activity could be detected in human liver tissue.The present report describes experiments in which the level of the sphingomyelin-cleaving enzyme in liver and kidney tissue obtained from six patients with the classic infantile form of Niemann- Pick disease8 is compared with the values found in a liver biopsy sample from a normal human adult and liver and kidney tissue of patients with various other dis- orders.Materials and Methods.-Sphingomyelinlabeled with C14 in the methyl carbon atoms of the choline portion of the molecule was synthesized as described previously.7Samples of liver and kidney tissue were homogenized in 10 vol of 0.25 M sucrose with an all-glass TenBroeck homoge- nizer and centrifuged at 600 X g for 12 min.Suitable aliquots of the supernatant suspensions were