Properties of the residual α-galactosidase activity in the tissues of a fabry hemizygote

Abstract The properties of the residual α-galactosidase activity in kidney, liver, spleen, fibroblasts and urine of a Fabry hemizygote have been studied using p -nitrophenyl-α-galactoside and 4-methylumbelliferyl-α-galactoside as substrates. In addition, α-galactosidase activity in urine has been determined with ceramidetrihexoside as substrate. The residual α-galactosidase activity of Fabry, measured with artificial substrate, is stimulated (6–35%) by myo -inositol and only slightly inhibited by melibiose (7–17%) in all the materials used. In contrast, the α-galactosidase of normal tissues and urine is inhibited (36–48%) by myo -inositol and inhibited to a much greater extent (40–50%) by melibiose. The K m for artificial substrate of the residual activity of Fabry is higher than that of the α-galactosidase in normal kidney, liver, spleen, fibroblasts and urine. The residual activity of Fabry is generally more stable to heating than the activity in the normal materials, although exceptions were noted. When these properties are compared with those of the α-galactosidase isoenzymes in normal tissues and body fluids, the residual activity of Fabry material seems to be very similar to the minor component of normal tissue (α-galactosidase B). Moreover, the pH optimum curve of this minor component and of the Fabry α-galactosidase in urine are similar, whereas the major isoenzyme (α-galactosidase A) shows a curve much more like that of normal urine. The findings with ceramidetrihexoside as substrate indicate a possible discrepancy. α-Galactosidase A hydrolyses ceramidetrihexoside, Fabry urine preparation does not. However, α-galactosidase B of normal urine shows a slight but definite ceramidetrihexosidase activity. No contamination of the B preparation with α-galactosidase A could be detected. The minimum hypothesis, supported by most of the experimental evidence is that the residual activity of Fabry and normal α-galactosidase B are identical.