The occurrence of two immunologically distinguishable beta-glucocerebrosidases in human spleen

Aerts, Johannes M. F. G.; Donker‐Koopman, Wilma E.; Vliet, M. K. Van Der; Jonsson, Lisbeth; Ginns, Edward I.; Murray, Gary J.; Barranger, John A.; Tager, J. M.; Schram, A. W.

doi:10.1111/j.1432-1033.1985.tb09058.x

Cited by 72 publications

(73 citation statements)

References 25 publications

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“…The extracts were prepared by homogenising the tissue or cells in 50 mM potassium phosphate buffer (pH 6.5) containing 0.25% (v/v) Triton X-100, as described in Materials and Methods. Form I and form 11 glucocerebrosidase were measured exactly as described in [22]. …”

Section: Isolation Of Activator Proteinmentioning

confidence: 99%

“…Triton X-1 00 extracts of various human tissues and cultured skin fibroblasts were prepared and the content of form I and form I1 glucocerebrosidase was determined as described in [22]. The presence of the two forms of glucocerebrosidase was demonstrated in extracts of all tissues examined (Table 1).…”

Section: Distribution Ofform I and F O R M 11 Glucocerebrosidase In mentioning

confidence: 99%

“…In addition, we have recently shown [22] that extracts of human spleen contain two forms of glucocerebrosidase that can be distinguished by immunotitra-tion experiments using polyclonal or monoclonal anti-@la-cental glucocerebrosidase) antibodies bound to protein-ASepharose 4B beads. Form I glucocerebrosidase binds to the immobilised antibodies and is precipitated, whereas form I1 glucocerebrosidase does not 1221.…”

mentioning

confidence: 99%

“…Form I glucocerebrosidase binds to the immobilised antibodies and is precipitated, whereas form I1 glucocerebrosidase does not 1221. When denatured, however, both forms react with anti-(placental glucocerebrosidase) antibodies [22]. The two forms differ in isoelectric focussing patterns and in degree of stimulation by sodium taurocholate of the hydrolysis of the artificial substrate 4-methylumbelliferyl-fl-glucoside [22].…”

mentioning

confidence: 99%

“…When denatured, however, both forms react with anti-(placental glucocerebrosidase) antibodies [22]. The two forms differ in isoelectric focussing patterns and in degree of stimulation by sodium taurocholate of the hydrolysis of the artificial substrate 4-methylumbelliferyl-fl-glucoside [22]. Both forms of glucocerebrosidase are deficient in spleens from patients with Gaucher disease, the activity of form I being 5-15% and that of form I1 25 -50% of the respective activities in extracts of control spleens 1221.…”

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confidence: 99%

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Relationship between the two immunologically distinguishable forms of glucocerebrosidase in tissue extracts

et al. 1987

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Extracts of human spleen contain two immunologically distinguishable forms of glucocerebrosidase: form I is precipitable by polyclonal or monoclonal anti‐(placental glucocerebrosidase) antibodies, whereas form II is not [Aerts, J. M. F. G., Donker‐Koópman, W. E., Van der Vliet, M. F. K., Jonsson, L. M. V., Ginns, E. I., Murray, G. J., Barranger, J. A., Tager, J. M. & Schram, A. W. (1985) Eur. J. Biochem. 150, 565–574]. The proportion of form II glucocerebrosidase was high in extracts of spleen, liver and kidney and low in extracts of brain, placenta and fibroblasts. Furthermore, the proportion of form II enzyme was higher in a detergent‐free aqueous extract of spleen than in a Triton X‐100 extract of total spleen or splenic membranes. When form II glucocerebrosidase in a splenic extract was separated from form I enzyme by immunoaffinity chromatography and stored at 4°C, a gradual conversion to form I enzyme occurred. The conversion was almost immediate if 30% (v/v) ethylene glycol was present. In the denatured state both forms of glucocerebrosidase reacted with anti‐(placental glucocerebrosidase) antibodies. Form I glucocerebrosidase was stimulated by sodium taurocholate or sphingolipid‐activator protein 2 (SAP‐2), whereas form II enzyme exhibited maximal activity in the absence of the effectors. The pH activity profile of form II glucocerebrosidase was almost identical to that of form I enzyme in the presence of SAP‐2. In the native state, form I glucocerebrosidase had a molecular mass of 60 kDa whereas that of form II glucocerebrosidase was about 200 kDa. After gel‐permeation high‐pertormance liquid chromatography of splenic extracts, the fractions with form II glucocerebrosidase contained material cross‐reacting with both anti‐(placental glucocerebrosidase) and anti‐(SAP‐2) antibodies. Preincubation of form I glucocerebrosidase with SAP‐2 at pH 4.5 led to masking of the epitope on glucocerebrosidase reacting with monoclonal anti‐(placental glucocerebrosidase) antibody 2C7. Furthermore, preincubation of form I glucocerebrosidase with monoclonal antibody 2C7 prevented activation of the enzyme by SAP‐2. We propose that form I glucocerebrosidase is a monomeric form of the enzyme, whereas form II glucocerebrosidase is a high‐Mr complex of the enzyme in association with sphingolipid‐activator protein 2.

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Section: Isolation Of Activator Proteinmentioning

confidence: 99%

Section: Distribution Ofform I and F O R M 11 Glucocerebrosidase In mentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Relationship between the two immunologically distinguishable forms of glucocerebrosidase in tissue extracts

et al. 1987

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Glycosphingolipide – Natur, Funktion und pharmakologische Modulierung

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et al. 2009

Angewandte Chemie

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Die Entdeckung der Glycosphingolipide wird im Allgemeinen Johan L. W. Thudichum zugeschrieben, der 1884 über die chemische Zusammensetzung des Gehirns publizierte. In seinen Studien isolierte er aus ethanolischen Hirnextrakten mehrere Verbindungen, die er als Cerebroside bezeichnete. Eine dieser Verbindungen, Phrenosin (heute als Galactosylceramid bekannt), unterwarf er einer sauren Hydrolyse, aus der drei Komponenten hervorgingen. Eine Komponente identifizierte er als Fettsäure, eine andere als Isomer zur D‐Glucose, heute als D‐Galactose bekannt. Die dritte Komponente mit “alkaloidaler Natur” gab Thudichum “viele Rätsel” auf, weshalb er sie Sphingosin nannte, nach dem mythologischen Rätsel der Sphinx. Derzeit sind Sphingolipide und ihre glycosidierten Derivate Gegenstand intensiver Forschung mit dem Ziel, ihre Funktion für die strukturelle Integrität der Zellmembran, ihre Teilnahme in Erkennungs‐ und Signalübertragungsvorgängen und besonders ihre Beteiligung an pathologischen Prozessen, die als Ursache menschlicher Krankheiten (z. B. von Sphingolipidosen und Typ‐2‐Diabetes) gelten, aufzuklären. Dieser Aufsatz wird auf neuere Befunde zur Biosynthese, Funktion und zum Abbau von Glycosphingolipiden im Menschen eingehen, mit Fokus auf das Glycosphingolipidglucosylceramid. Besondere Aufmerksamkeit richtet sich auf die klinische Bedeutung von Verbindungen, die mit den Faktoren des Glycosphingolipid‐Metabolismus wechselwirken.

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Glycosphingolipids—Nature, Function, and Pharmacological Modulation

et al. 2009

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The discovery of the glycosphingolipids is generally attributed to Johan L. W. Thudichum, who in 1884 published on the chemical composition of the brain. In his studies he isolated several compounds from ethanolic brain extracts which he coined cerebrosides. He subjected one of these, phrenosin (now known as galactosylceramide), to acid hydrolysis, and this produced three distinct components. One he identified as a fatty acid and another proved to be an isomer of D-glucose, which is now known as D-galactose. The third component, with an "alkaloidal nature", presented "many enigmas" to Thudichum, and therefore he named it sphingosine, after the mythological riddle of the Sphinx. Today, sphingolipids and their glycosidated derivatives are the subjects of intense study aimed at elucidating their role in the structural integrity of the cell membrane, their participation in recognition and signaling events, and in particular their involvement in pathological processes that are at the basis of human disease (for example, sphingolipidoses and diabetes type 2). This Review details some of the recent findings on the biosynthesis, function, and degradation of glycosphingolipids in man, with a focus on the glycosphingolipid glucosylceramide. Special attention is paid to the clinical relevance of compounds directed at interfering with the factors responsible for glycosphingolipid metabolism.

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The occurrence of two immunologically distinguishable beta-glucocerebrosidases in human spleen

Cited by 72 publications

References 25 publications

Relationship between the two immunologically distinguishable forms of glucocerebrosidase in tissue extracts

Relationship between the two immunologically distinguishable forms of glucocerebrosidase in tissue extracts

Glycosphingolipide – Natur, Funktion und pharmakologische Modulierung

Glycosphingolipids—Nature, Function, and Pharmacological Modulation

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