EVIDENCE FOR A HYBRID HEXOSAMINIDASE ISOENZYME IN HETEROZYGOTES FOR SANDHOFF DISEASE

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  • 1 January 1979
    • journal article
    • research article
    • Vol. 31  (3) , 281-289
Abstract
Patients with Sandhoff disease have < 5% of normal levels of serum or tissue hexosaminidase activity, and are thought to have a defect in the structural gene for the .beta.-chain of hexosaminidase (HEX). Heterozgotes for Sandhoff disease have .apprx. 50% of the total serum HEX activity of normals and > 75% of the HEX is heat-labile. In normals, only 55-65% of serum HEX is heat-labile. Serum HEX separates into 3 forms on DEAE cellulose chromatography: HEX A, a tetramer of 2.alpha.- and 2.beta.-chains, and HEX I and B composed solely of .beta.-chains. The DEAE chromatograms from normals and Sandhoff heterozygotes did not differ in the relative distribution of HEX activity between peaks. In normals, the HEX A peak was heat-labile (60.degree. C for 9 min), but HEX I and B were heat-stable. In Sandhoff heterozygotes, HEX I and B were only 50-53% heat-stable. The heterozygotes apparently synthesized a hybrid enzyme containing both mutant and wild-type .beta.-chains for HEX. The mutant .beta.-chain renders the isoenzyme less stable to heating.