Galactosylgalactosylglucosylceramide: Galactosyl hydrolase in normal human plasma and its absence in patients with fabry's disease

Multiple Forms of Glycosidases in the Normal and Pathological States

“…Mapes et al [39] recorded a bimodal pH curve for the activity of nor mal human plasma with peaks at 5.4 and 7.2, but no other reports of this 'neutral a-galactosidase' are available. While the plasma enzyme and that from a number of other sources is rather unstable, that form present in urine is quite stable and was demonstrated to be active on ceramide trihexoside by Rietra et al [40], A profound defect in the levels of this enzyme was recorded by Kint [41] in cases of Fabry's disease, with lowered levels in heterozygous fem ales.…”

Enzyme therapy in Fabry disease: differential in vivo plasma clearance and metabolic effectiveness of plasma and splenic alpha-galactosidase A isozymes.

“…In 1970, we reported the first clinical trial (10) based on the finding that normal plasma contained active a-GAL A (2). Single infusions of fresh normal plasma, containing about 6000 units of enzymatic activity, were administered to three patients with Fabry disease; the infused activity disappeared from the circulation with a half-life of about 95 min and approximately 50% of the circulating substrate was cleared for a period of several days (10,11).…”

“…Fabry disease, an inborn error of glycosphingolipid metabolism, results from the defective activity of the lysosomal hydrolase, a-galactosidase A (a-GAL A; a-D-galactosidase; a-D-galactoside galactohydrolase, EC 3.2.1.22) (1)(2)(3)(4). Trihexosylceramide [globotriaosylceramide; Gb3Cer; Gal(a1-4)Gal(31-4)-Glc(3l -')Cer], the enzyme's major glycosphingolipid substrate, accumulates in the plasma (5) and particularly in the vascular endothelial lysosomes (6)(7)(8) of hemizygous males afflicted with this X-linked disease.…”

Correction of the Enzymic Defect in Cultured Fibroblasts from Patients with Fabry's Disease: Treatment with Purified α-Galactosidase from Ficin

“…The studies of Neufeld et al [17] indicate that human lysosomal enzymes, partially purified from urine, retain the ability to "correct" enzymic deficiencies in fibroblasts from patients with mucopolysaccharide storage disorders. However, previous studies on mammalian a-galactosidases [2,13] have indicated a relatively low activity toward GL-3 compared with the ficin enzyme [29], whereas preparations from Aspergillus niger or Moriterella vinacea [7] showed high reactivity toward the synthetic a-galactoside but none toward GL-3. The feasibility of administering to a patient an enzyme derived from a plant would appear to be extremely unlikely but a precedent does exist from in vivo studies on a child with type II glycogen storage disease, with the use of glycogen-degrading enzymes prepared from A. niger [8].…”

“…Further, Romeo and Migeon [20] have demonstrated that fibroblasts from obligate heterozygotes could be cloned into normal and affected cell strains, the heterozygote cultures with 50% of normal enzymic activity. Mapes et al [13] have demonstrated the presence of GL-3-a-galactosidase activity in normal human plasma and suggested that plasma infusion might be a useful therapeutic measure for treating this visceral storage disease. The initial success of enzyme replacement by plasma infusion [14], which may have stimulated the de novo synthesis of enzyme, has prompted the use of organ transplantation (such as renal) as a means of more permanent enzyme replacement [18,23].…”