A new from of residual hexosaminidase activity in infantile Tay Sachs disease fibroblasts

Fibrolast cells lines obtained from five patients with the early onset form of Tay Sachs disease (TSD) possess a species of β-N-acetylhexosaminidase (Hex) which is more anionic than Hex B but which is stable to heating under conditions which completely inactivate Hex A. This speices, which comprised between 3 and 20% of th total hexosaminidase acitivity in homozygous TSD fibroblasts, appeared to be unstable and upon isoelectric focussing produced a mixture of Hex B (pI=7.2) and an isozayme with a pI of 6.2. This intermediate form of hexosaminidase was not seen in two normal fibroblast cell lines but was observed following anion exchange chromatography of extracts of fibroblast cell lines obtained from two obligate heterozygotes. A species of hexosaminidase with the same chromatographic properties, thermostability and isoelectric point as the intermediate form found in fibroblasts with the TSD genotypes can be recovered after anion exchange chromatography of a partially purified preparation of human liver Hex A that had been treated with merthiolate. We hypothesize that in TSD cells a form of the β subunit which is usually incorporated into Hex A accumulates due to the absence of a subunits. This form of the β subunit is more anionic than the β subunit found in Hex B. In the absence of α subunits these anionic β subunits form tetramers with a pI = 6.2. This form of the enzyme is unstable in the presence of cellular proteases and may be modified to Hexosaminidase B.