Neuropathic Gaucher's Disease with Normal 4− MethyIumbelliferyl-β-glucosidase Activity in the Liver

Ōwada, Misao; Sakiyama, Takeshi; Kitagawa, Teruo

doi:10.1203/00006450-197705000-00004

Cited by 43 publications

(26 citation statements)

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“…This is especially true because of the importance for identification of heterozygotes and the capability of intrauterine detection. Although an assay with an artificial substrate has the advantage of simplicity, it is not reliable in some cases of Gaucher's disease, especially when liver is the source of diagnostic material (Patrick, 1965;Broadhead and Butterworth, 1977;Owada et al, 1977). This is probably due to f-glucosidase activity of a distinct enzyme, neutral ,B-galactosidase, which possesses activity towards both aryl-,B-galactosides and aryl-,B-glucosides at pH 5-6.…”

Section: Discussionmentioning

confidence: 99%

“…Deficiency of /3-glucosidase activity (EC 3.2.1.21) towards synthetic substrates such as 4-methylumbelliferyl fl-glucoside and p-nitrophenyl g-glucoside has also been reported in patients with Gaucher's disease (Patrick, 1965;Kampine et al, 1967;Beutler and Kuhl, 1970). Of interest, several cases of Gaucher's disease have been reported in which patients could not be distinguished from controls when liver homogenates were assayed with an artificial substrate (Patrick, 1965;Broadhead and Butterworth, 1977;Owada et al, 1977).…”

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confidence: 99%

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Pitfalls in the use of artificial substrates for the diagnosis of Gaucher's disease.

Ben‐Yoseph¹,

Nadler²

1978

J Clin Pathol

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A patient with Gaucher's disease is described, in whom the disease could not be diagnosed enzymically in liver and leucocytes using artificial substrate 4-methylumbelliferyl beta-glucoside. Normal activity was found in the liver, and about 60% of control activity was determined in the patient's leucocytes. In contrast, when [14C]-N-stearoyl glucocerebroside was employed as a substrate, activity as low as 5% of control has been found in all the proband's tissues, and carrier levels were determined in the proband's parents and maternal uncle.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Pitfalls in the use of artificial substrates for the diagnosis of Gaucher's disease.

Ben‐Yoseph¹,

Nadler²

1978

J Clin Pathol

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“…Recently, the reliability of using the fluorogenic substrate, 4MUGP, and visceral tissues as the source of enzyme in the diagnosis of Gaucher's disease had been studied by Owada et al (21). It was reported that in neuropathic Gaucher's disease, normal P-glucosidase activity was detected in the liver of one group of patients, whereas deficient activity was detected in another group (21).…”

Section: Discussionmentioning

confidence: 99%

“…It was reported that in neuropathic Gaucher's disease, normal P-glucosidase activity was detected in the liver of one group of patients, whereas deficient activity was detected in another group (21). Therefore, the deficiency of 4MUGP-P-glucosidase in liver (and possibly in spleen) may not account for the accumulation of glucocerebroside, and the deficiency of glucocerebroside-P-glucosidase activity, probably existing within the reticuloendothelial cells, may be more essential for the accumulation (21).…”

Section: Discussionmentioning

confidence: 99%

Gaucher's Disease. I. Solubilization and Electrophoresis of β-Glucosidase from Leukocytes and Cultured Fibroblasts

Choy

Davidson

1978

Pediatr Res

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SummaryIn order to determine unambiguously the presence of multiple forms of P-glucosidase in normal leukocytes and fibroblasts and the form(s) present in Gaucher's disease, we had to devise techniques to separate P-glucosidase from the lysosomal membrane in a catalvticallv active form and to visualize the isozvmes electrophoretically. separation of relatively stable enzyme from the membrane was not achieved until leukocyte and fibroblast suspensions were freeze-thawed consecutively 10 times. After ~ello~elelectro-phoresis of normal leukocyte extracts, two distinct and discrete bands of P-glucosidase activity, which migrated toward the anode, were observed using the fluorogenic substrate 4-methylumbelliferyl-P-D-glucopyranoside. In patients with juvenile onset Gaucher's disease, all of the leukocyte P-glucosidase activity remained at the origin. The electrophoretic pattern of P-glucosidase from normal cultured skin fibroblasts showed only one fluorescent band of a-glucosidase activity which also migrated toward the anode, but with lesser mobility than the leukocyte bands. In fibroblast extracts of patients with Gaucher's disease, P-glucosidase activity could not be visualized after electrophoresis, even though prior to electrophoresis these extracts had 15-35% of normal activity.

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“…Une MeUmb-P-glucosidase non specifique membranaire hydrolysant le substrat artificiel, acidolabile, conserve son activite dans les cellules lymphoblastoides en culture provenant de maladie de Gaucher [14], dans le foie de certains cas de maladie de Gaucher [15] et dans la rate de Gaucher [16].…”

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Propriétés des formes moléculaires de la β-glucosidase et de la β-glucocéréhrosidase de rate humaine normale et de maladie de Gaucher

Maret

Douste‐Blazy

Salvayre

et al. 2005

European Journal of Biochemistry

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Properties of the Molecular Forms of β‐Glucosidase and β‐Glucocerebrosidase from Normal Human and Gaucher Disease Spleen Comparative studies of β‐glucosidases and β‐glucocerebrosidases from normal human and Gaucher disease spleen have allowed to identify three enzymatic groups on the basis of their subcellular localization (soluble or membrane‐bound), enzymatic and genetic properties. β‐Glucocerebrosidase cleaves both the natural substrate, β‐glucocerebroside and the artificial substrate, methylumbelliferyl(MeUmb)‐β‐glucoside. A minor part (25%) is soluble in water whereas 75% of the total activity is membrane‐bound and can be solubilized by 0.25% Triton X‐100. Using preparative electrofocusing, the soluble β‐glucocerebrosidase shows two molecular forms (pI 5.2 ± 0.2 and 6.4 ± 0.2). Exactly the same forms are found for the membrane‐bound β‐glucocerebrosidase solubilized by Triton X‐100. All these molecular forms display the same enzymatic properties: optimum pH of 5.4, heat‐stability at 42° C, Km values of 3.7 ± 0.5 mM for the artificial substrate in the presence of sodium taurocholate and 0.06 ± 0.01 mM for the natural substrate. In addition they are activated at the same extent (600%) by sodium taurocholate. Furthermore, these two molecular forms are coded by the same gene since both are deficient in type I non neuropathic Gaucher disease. The soluble non specific MeUmb‐fl‐glucosidase catalyses the hydrolysis of the artificial substrate but not of the natural substrate and is focused in one single peak (pI 4.7 ± 0.2) different from the two forms of β‐glucocerebrosidase discussed above. It is strongly inhibited by sodium taurocholate, weakly by Triton X‐100 and is heat‐labile at 42° C. No deficiency is detected in the case of type I Gaucher disease reported here. it is thus suggested that this enzyme corresponds to a gene different from that coding for β‐glucocerebrosidase. The membrane‐bound non specific MeUmb‐β‐glucosidase also hydrolyses the artificial substrate but not the natural substrate. This enzyme differs from the soluble one with regard to its heat‐stability at 42° C and its. strong inhibition by Triton X‐100. On the other hand, the membrane‐bound non specific MeUmb‐β‐glucosidase differs from the membrane‐bound β‐glucocerebrosidase in its heat‐stability at 50° C, its substrate specificity and the sodium‐taurocholate effect. This enzyme activity is about normal in Gaucher disease and is thus coded by a gene different from the β‐glucocerebrosidase one.

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Neuropathic Gaucher's Disease with Normal 4− MethyIumbelliferyl-β-glucosidase Activity in the Liver

Cited by 43 publications

References 1 publication

Pitfalls in the use of artificial substrates for the diagnosis of Gaucher's disease.

Pitfalls in the use of artificial substrates for the diagnosis of Gaucher's disease.

Gaucher's Disease. I. Solubilization and Electrophoresis of β-Glucosidase from Leukocytes and Cultured Fibroblasts

Propriétés des formes moléculaires de la β-glucosidase et de la β-glucocéréhrosidase de rate humaine normale et de maladie de Gaucher

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