An electrophoretic variant of beta-galactosidase with altered catalytic properties in a patient with GM1 gangliosidosis.

Abstract

In nine patients with GM, gangliosidosis, liver ganglioside GM1 B-galactosidase (EC 3.2.1.23) activity ranged from less than 0.01% to 0.05% of normal. In a tenth patient's liver, much higher activity was found (0.5% of normal). In this patient the residual enzyme had the same molecular weight as fl-galactosidase A, the major form of 6-galactosidase of normal human liver. No activity was found that corresponded to j3-galactosidase B, the minor form of human liver #-galactosidase. On starch gel electrophoresis, the patient's enzyme migrated less anodally than normal j3-galactosidase A, both before and after treatment with neuraminidase. P-Galactosidase from the patient had a Km that was higher than normal; 5-fold higher with ganglioside GM, and 2-fold higher with 4. methylumbelliferyl j0-galactoside. The patient's enzyme crossreacted immunologically with normal ,6-galactosidase A and had about 100-fold more antigenic activity per unit catalytic activity than the normal enzyme. The results indicate that in this patient a P-galactosidase A protein with altered charge and altered catalytic properties was present in relatively normal amounts, the first electrophoretic variant reported for a patient with a lysosomal hydrolase deficiency.

Molecular genetics of GM1β‐galactosidase

“…Dr. Norden and I (Norden & O'Brien 1975) studied in detail one unusual patient (CE) with a phenotype similar to Type 2.…”

Filipin recognizes both GM1 and cholesterol in GM1 gangliosidosis mouse brain

“…These fi ndings suggested that cholesterol was a secondary storage molecule to GM1 in this disease. GM1 gangliosidosis is an autosomal recessive glycosphingolipid storage disorder caused by mutations in lysosomal ␤ -galactosidase activity (18)(19)(20). The loss or reduction of ␤ -galactosidase activity results in a failure to cleave the terminal galactosyl residue of ganglioside GM1, leading to excessive central nervous system storage of GM1 and its asialo derivative, GA1 (21)(22)(23)(24)(25).…”

GM1‐gangliosidosis: A molecular abnormality of acid β‐galactosidase in fibroblasts

“…A molecular abnormality of 13-galactosidase was reported in a case of GMt-gangliosidosis with an abnormal electrophoretic mobility of the residual enzyme activity (Norden and O'Brien, 1975). However, no other direct evidence has been presented with respect to the structure of the inactive enzyme molecules in this disease.…”