Cerebroside Synthesis in Gaucher's Disease*

Familial lipodystrophic conditions, such as Gaucher's, Niemann-Pick, and Tay-Sachs disease, are characterized by the intracellular accumulation of abnormally large quantities of sphingolipids. In Gaucher's disease, the offending lipids are cerebrosides, while Niemann-Pick and Tay-Sachs diseases are characterized by the accumulation of sphingomyelin and gangliosides, respectively. In Gaucher's and Niemann-Pick disease, involvement of the reticuloendothelial system is extensive, and splenomegaly and hepatomegaly are frequently observed. Lieb in 1924 ( 1 ) identified the lipid stored in reticuloendothelial cells in a case of Gaucher's disease as a cerebroside. His findings were supported by other investigators (2, 3), and eventually Halliday, Deuel, Tragerman and Ward (4) and Rosenberg and Chargaff (5) presented evidence that the accumulated cerebrosides in Gaucher's disease contained predominantly glucose instead of the high content of galactose usually present in cerebrosides. It was felt that techniques developed in this laboratory for studies of the biosynthesis of sphingosine and cerebrosides might be useful for investigations of cerebroside formation in tissue samples obtained from patients with Gaucher's disease. The data obtained by Brady and Koval (6), Burton, Sodd and Brady (7), and Cleland and Kennedy (8) indicate that cerebroside synthesis probably occurs in the following fashion: palmitic aldehyde + serine -sphingosine + C02; sphingosine + uridinediphosphate galactose -> psychosine + uridinediphosphate; psychosine + fatty acid -* cerebroside. Since purified enzyme systems which catalyze the biosynthesis of cerebrosides were not available, tissue slices were employed in the present investigations to study the formation of these sphingolipids. Tissue was occasionally available from patients who were sple-