Substrate Specificity of Hexosaminidase a Isolated from the Liver of a Patient with a Rare Form (AB Variant) of Infantile GM2 Gangliosidosis and Control Tissues
An inheritable deficiency of hexosaminidase A and A and B causes neuronal storage of glycolipids in patients with the B variant (Tay-Sachs disease) and 0 variant form, respectively, of infantile GM2 gangliosidosis. The same glycolipids, the GM2 ganglioside and its GA2 asialo-derivative, accumulate also in the neural tissues of patients with the AB variant form of the disease (1). In this form, however, a deficient activity of hexosaminidase A could not be demonstrated using synthetic substrates. In order to test the possibility of a mutant hexosaminidase A occurring in patients with this form of GM2 gangliosidosis, the enzyme obtained from the liver of an autopsy case of this disease variant was purified to homogeneity and characterized. Purification was achieved by affinity chromatography using a newly synthesized selective adsorbent ((6-Aminohexyl)-1-thio-2-acetamido-2-deoxy-ß-D-galactopyranoside) as substrate analog (2). The ligand has been shown to possess a competitive inhibitory effect (Ki = 0.17 mM) upon the enzyme under study.
KeywordsAutopsy Case Synthetic Substrate Disease Variant Substrate Analog Deficient Activity
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