PROPERTIES OF MULTIPLE MOLECULAR-FORMS OF ALPHA-GALACTOSIDASE AND ALPHA-N-ACETYLGALACTOSAMINIDASE FROM NORMAL AND FABRY LEUKOCYTES

In normal human leukocytes three forms of methylumbelliferyl α‐galactosidase (EC 3.2.1.22) are separated using preparative electrofocusing: form I (pI 5.00) and form II (pI 4.5) which are known in other tissues as α‐galactosidase A and α‐galactosidase B respectively, and a new major form that we name form IV (pI 3.95) which is characteristic of leukocytes. In normal human leukocytes only one molecular form of p‐nitrophenyl α‐N‐acetylgalactos‐aminidase corresponding to the form II of methylumbelliferyl α‐galactosidase (or α‐galactosidase B) is present. In leukocytes from patients with Fabry disease the deficient activity corresponds to forms I and IV, whereas the residual activity corresponds to form II. This single residual form seems to be identical to the normal p‐nitrophenyl α‐N‐acetylgalactosaminidase. In leukocytes the molecular forms of methylumbelliferyl α‐galactosidase and p‐nitrophenyl α‐N‐acetylgalactosaminidase from normal subjects and patients with Fabry disease can be divided into two groups on the basis of their enzymatic and genetic properties. One group is made of form I (isoenzyme A) and of the new major form IV: heat‐labile, with close Km values for MeUmb‐Gal (Km I = 2.1 × 10−3 M and Km IV = 1.9 × 10−3 M), inhibited by α‐galactosides and mesoinositol and inactive in Fabry disease (coded by the same X‐linked gene). The other group only concerns methylumbelliferyl α‐galactosidase form II (isoenzyme B), or α‐N‐acetylgalactosaminidase. This form II from normal subjects has the same properties as the residual one from Fabry disease: heat‐stable, close Km values for MeUmb‐Gal (Km II = 5.1 × 10−3 M and KmF = 5.5 × 10−3 M) and for Nph‐GalNAc (Km normal = 1.7 × 10−3 M and Km Fabry = 2.0 × 10−3 M), inhibited by α‐galactosides and by α‐N‐acetylgalactosaminides. This form is coded by a gene different from the X‐linked gene. Copyright © 1979, Wiley Blackwell. All rights reserved