TY - JOUR
T1 - Sulfogalactocerebroside and bis-(monoacylglyceryl)-phosphate as activators of spleen glucocerebrosidase
AU - Prence, Elizabeth M.
AU - Garrett, Kevin O.
AU - Panitch, Howard
AU - Basu, Alakananda
AU - Glew, Robert H.
AU - Wherrett, John R.
AU - Huterer, Srebrenka
N1 - Funding Information:
This work was supported by grant AM 31357 from the United States Public Health Service, National institutes of Health, and by a grant from the Medical Research Council of Canada.
PY - 1986/4/30
Y1 - 1986/4/30
N2 - Sequential extraction of human spleen membranes with sodium cholate and n-butanol removes endogenous lipids and renders glucocerebrosidase activity dependent upon exogenous acidic lipids (e.g., phosphatidylserine, gangliosides) and a heat-stable activator protein (HSF). In the present report, we show that two previously untested lysosomal acidic lipids, namely sulfogalactocerebroside and bis-(monoacylglyceryl)-phosphate (BMP), also activate normal human glucocerebrosidase. In addition, sulfogalactocerebroside also markedly enhanced the activity of glucocerebrosidase isolated from a patient with type 1 (non-neuronopathic) Gaucher's disease, resulting in a specific activity which was 60-80% that of control glucocerebrosidase. Furthermore, when the sulfolipid was used as the activator, glucocerebrosidase from the type 1 patient was 30 times more active than the corresponding glucocerebrosidase from a person with type 2 (neuronopathic) Gaucher's disease. In contrast, the two BMPs, one rich in C26 saturated fatty acid and another rich in C18 unsaturated fatty acids, were relatively poor activators of both mutant glucocerebrosidases while providing excellent reconstitution of control activity.
AB - Sequential extraction of human spleen membranes with sodium cholate and n-butanol removes endogenous lipids and renders glucocerebrosidase activity dependent upon exogenous acidic lipids (e.g., phosphatidylserine, gangliosides) and a heat-stable activator protein (HSF). In the present report, we show that two previously untested lysosomal acidic lipids, namely sulfogalactocerebroside and bis-(monoacylglyceryl)-phosphate (BMP), also activate normal human glucocerebrosidase. In addition, sulfogalactocerebroside also markedly enhanced the activity of glucocerebrosidase isolated from a patient with type 1 (non-neuronopathic) Gaucher's disease, resulting in a specific activity which was 60-80% that of control glucocerebrosidase. Furthermore, when the sulfolipid was used as the activator, glucocerebrosidase from the type 1 patient was 30 times more active than the corresponding glucocerebrosidase from a person with type 2 (neuronopathic) Gaucher's disease. In contrast, the two BMPs, one rich in C26 saturated fatty acid and another rich in C18 unsaturated fatty acids, were relatively poor activators of both mutant glucocerebrosidases while providing excellent reconstitution of control activity.
KW - Gaucher's disease
KW - Glucocerebrosidase
KW - Heat-stable factor
KW - Sphingolipidosis
KW - Sulfogalactocerebroside
KW - bis-(Monoacylglyceryl)-phosphate
UR - http://www.scopus.com/inward/record.url?scp=0022542365&partnerID=8YFLogxK
U2 - 10.1016/0009-8981(86)90151-8
DO - 10.1016/0009-8981(86)90151-8
M3 - Article
C2 - 3085988
AN - SCOPUS:0022542365
SN - 0009-8981
VL - 156
SP - 179
EP - 189
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
IS - 2
ER -