The isoenzyme hexosaminidase A (HEXA) is composed of subunits α and β and breaks down molecules containing terminal N-acetyl hexosamines.Tay-Sachs disease is caused by a recessively inherited loss-of-function mutation in the gene coding for the α subunit, which is the subunit that hydrolyzes the lipid GM2 ganglioside.Accumulation of this lipid in the brain leads to progressive deterioration of the nervous system and death, usually by age 4.The most common mutation in the HEXA gene is an insertion of four base pairs in exon 11 that creates a nonfunctional truncated protein.HEXA activity is 0 to 6 percent in homozygous recessives and 7 to 35 percent in heterozygous carriers, compared with noncarriers (100 percent).What evidence presented here strongly suggests that this truncated α subunit can still associate with the normal β subunit, thereby inhibiting its association with functional α subunit?

Question

Quizplus · Accepted Answer

The fact that HEXA activity in heterozygous carriers is significantly less than 50 percent of that in noncarriers suggests that the presence of the truncated α subunit interferes with the normal function of the enzyme, likely by still being able to associate with the β subunit but not function properly, thus inhibiting the formation of fully functional HEXA enzyme complexes.

The Isoenzyme Hexosaminidase a (HEXA) Is Composed of Subunits α