An Investigation of the Metabolism of Tay-Sachs Ganglioside Specifically Labeled in Critical Portions of the Molecule
Investigations which provided for a demonstration of an enzymatic deficiency in Tay-Sachs disease varied considerably in design from the basic pattern of experimentation which proved so useful for unravelling the metabolic abnormalities in related disorders of lipid metabolism. For example, in order to elucidate the etiology of Gaucher’s disease, Niemann-Pick disease, and Fabry’s disease, the principal sphingolipid which accumulates in the tissues of patients with these disorders was labeled with radiocarbon-14C or radiohydrogen-3H in a critical portion of the molecule. The metabolism of these labeled compounds was then examined in the following fashion. Enzymes which catalyzed the initial step in the catabolism of the accumulating substances were identified and partially purified from appropriate mammalian tissues. The conditions which influenced the activity of these enzymes were ascertained. The optimal pH for the reactions was determined, the Michaelis constant for each enzyme was defined, and the products of the reactions were identified. When these parameters were clearly established in control human tissue preparations, the activity of the enzyme suspected of being involved in the pathogenesis of the disease was determined in similar specimens obtained from patients with these disorders of lipid metabolism. This technique was used with success for identifying the deficiency of glucocerebrosidase in Gaucher’s disease, sphingomyelinase in Niemann-Pick disease, and ceramidetrihexosidase in Fabry’s disease(1).
KeywordsSialic Acid Lipid Storage Disease Sachs Disease Human Muscle Tissue Hexosaminidase Activity
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