The interrelations between high- and low-molecular weight forms of normal and mutant (Krabbe-disease) galactocerebrosidase

Galactocerebrosidase (beta-d-galactosyl-N-acylsphingosine galactohydrolase; EC 3.2.1.46) activity of brain and liver preparations from normal individuals and patients with Krabbe disease (globoid-cell leukodystrophy) have been separated by gel filtration into four different molecular-weight forms. T...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical journal 1980-07, Vol.189 (1), p.9-15
Main Authors: Ben-Yoseph, Y, Hungerford, M, Nadler, H L
Format: Article
Language:English
Subjects:
Brain - enzymology
Chromatography, Gel
Electrophoresis, Polyacrylamide Gel
Enzymes and Enzyme Kinetics
Galactosidases - metabolism
Galactosylceramidase - immunology
Galactosylceramidase - metabolism
Humans
Immunoassay
Leukodystrophy, Globoid Cell - enzymology
Liver - enzymology
Macromolecular Substances
Molecular Weight
Precipitin Tests
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Galactocerebrosidase (beta-d-galactosyl-N-acylsphingosine galactohydrolase; EC 3.2.1.46) activity of brain and liver preparations from normal individuals and patients with Krabbe disease (globoid-cell leukodystrophy) have been separated by gel filtration into four different molecular-weight forms. The apparent mol.wts. were 760000+/-34000 and 121000+/-10000 for the high- and low-molecular-weight forms (peaks I and IV respectively) and 499000+/-22000 (mean+/-s.d.) and 256000+/-12000 for the intermediate forms (peaks II and III respectively). On examination by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, the high- and low-molecular-weight forms revealed a single protein band with a similar mobility corresponding to a mol.wt. of about 125000. Antigenic identity was demonstrated between the various molecular-weight forms of the normal and the mutant galactocerebrosidases by using antisera against either the high- or the low-molecular-weight enzymes. The high-molecular-weight form of galactocerebrosidase was found to possess higher specific activity toward natural substrates when compared with the low-molecular-weight form. It is suggested that the high-molecular-weight enzyme is the active form in vivo and an aggregation process that proceeds from a monomer (mol.wt. approx. 125000) to a dimer (mol.wt. approx. 250000) and from the dimer to either a tetramer (mol.wt. approx. 500000) or a hexamer (mol.wt. approx. 750000) takes place in normal as well as in Krabbe-disease tissues.
ISSN:0264-6021
1470-8728
DOI:10.1042/bj1890009