Gargoylism: hydrolysis of β-galactosides and tissue accumulation of galactose- and mannose-containing compounds

Abstract

A B S T R A C T The sugars present in hydrolyzed extracts of human liver and brain were analyzed by gasliquid chromatography after conversion to their alditol acetates. The samples analyzed were obtained from control subjects, patients with gargoylism, and patients with a few other kinds of storage disorders. Accumulation of galactose was demonstrated in the liver and the brain of two patients with gargoylism, and in the liver samples, high levels of mannose were found too. We also studied the hydrolysis of a number of galactosides by homogenates from different tissues in the control subjects and in the patients. Separation methods and kinetic studies demonstrated the presence in normal human tissues of two different f-galactosidases, which we call enzyme A and enzyme B, respectively. Enzyme A hydrolyzed all the P-galactosides tested. Enzyme B hydrolyzed the synthetic substrates tested (4-methylumbelliferyl-, p-nitrophenyl-, o-nitrophenyl-, and phenyl-P-galactoside) but not the natural substrates tested (ceramide-i3-galactoside, ceramide lactoside, transferrin glycopeptide, and keratan sulfate). Enzyme B also exerted P-glucosidase activity. In various tissues from patients with gargoylism, deficiency of P-galactosidase A could be demonstrated.It is suggested that the high level of galactose found in the hydrolyzed extracts of tissues from gargoylism patients is due to storage of galactose-rich glycosaminoglycans and glycopeptides, and that this storage is a result of the deficiency of P-galactosidase A.The high level of mannose in the liver from gargoylism patients seems to indicate storage of glycopeptide, adding a new group of substances to those known to be stored in gargoylism.

Krabbe's globoid cell leucodystrophy. Studies on galactosylceramide beta-galactosidase and non-specific beta-galactosidase of leucocytes, cultured skin fibroblasts, and amniotic fluid cells.

“…3c); a minor peak at pH 4.6 and a major peak at pH 4.9 to 5.1. This agrees well with the results of Suzuki and Suzuki (1974b) who used human liver, but is contrary to an earlier report by Hultberg, Ockerman, and Dahlqvist (1970) who also used liver, but a high speed supernatant fraction which has certain inherent drawbacks. The 4-MU,B-galactosidase activity appeared as a similar profile to the cerebrosidase though the lower pI form was not always well separated from the major band.…”

“…The 4-MU,B-galactosidase activity appeared as a similar profile to the cerebrosidase though the lower pI form was not always well separated from the major band. No peak was seen at pH 4.2 as reported by Hultberg et al (1970) and Suzuki and Suzuki (1974b) for the hepatic enzyme. When the GLD fibroblast extract was focused (Fig.…”

Mannosidosis: Clinical, Fine‐structural and Biochemical Findings in Three Cases

“…tural methods alone (2). In our cases the vacu- a Combined mean values (range) from dckerman (16) and Hultberg et al (7).…”

PROPERTIES OF FIVE ACID HYDROLASES IN HUMAN SKIN FIBROBLAST CULTURES Possible Use in the Diagnosis of Inborn Lysosomal Diseases

“…Gel filtration (Sephadex G-150, column 70 x 3 cm, Pharmacia, Uppsala, Sweden) and isoelectric focusing (commercial equipment, LKB-Produkter, Stockholm, Sweden) of soluble fibroblast fractions (crude hornogenate centrifuged at 100000 g for 60 min, supernatant used as enzyme source) were performed as described elsewhere (8). Ceramide-galactosidase was measured as in other tissues (7). 4-Methylumbelliferyl-glycosidic substrates (Koch-Light Labs, Colnbrook, Bucks, England) were used for P-galactosidase (P-D-galactoside galactohydrolase, EC 3.…”