The Inhibitory Action of Glycosaminoglycans on Brain Sialidase

Heijlman, J.

doi:10.1042/bst0020638

Cited by 4 publications

(3 citation statements)

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“…It had been observed that sialoglycopeptides prepared without removal ofglycosaminoglycans showed little reaction with calf brain neuraminidase and that chondroitin sulphate and to a greater extent heparin inhibited the enzyme action when gangliosides or sialoglycopeptides were used as substrates (Heijlman, 1974). Similar observations that the presence of sulphated glycosaminoglycans induced a strong pHdependent inhibition of some 30 lysosomal enzymes including neuraminidase has also been reported (Avila & Convit, 1975, 1976.…”

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confidence: 56%

Neuraminidase inhibition by chemically sulphated glycopeptides

Mian¹,

Anderson²,

Kent³

1979

Biochemical Journal

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Chemically sulphated glycopeptides (derived from pig duodenal mucosa) inhibited Clostridium perfringens neuraminidase (EC 3.2.1.18) activity in a pH-dependent manner. Analysis of inhibition kinetics data indicated that, although the enzyme inhibition could not be categorized into any of the classical types of inhibition, it could be interpreted as a function of the size and shape of the substrates used. The enzyme activity was inhibited by 86% and 40% when tested with bovine submaxillary-gland mucin (mol. wt. 4 x 10(5)-40 x 10(5) and N-acetylneuraminyl-lactose (mol. wt. 633) as substrates respectively. Presence of sulphated glycopeptide did not affect the binding of N-acetylneuraminic acid (mol. wt. 309), a competitive inhibitor of Vibrio cholerae neuraminidase, to the enzyme active site. The enzyme inhibition was thus considered to be due to steric hindrance as a consequence of the non-specific interactions between the enzyme molecule and polyanionic sulphated glycopeptide affecting the differential accessibility of the substrate molecules to the enzyme active site. The enzyme-inhibitor interaction could be suppressed by rapid and many-fold dilution of the reaction mixture, by concurrent addition of the inactive enzyme or by partial removal of the sulphate esters from the sulphated glycopeptide molecule by the action of Helix pomatia arylsulphatase (EC 3.1.6.1).

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confidence: 56%

Neuraminidase inhibition by chemically sulphated glycopeptides

Mian¹,

Anderson²,

Kent³

1979

Biochemical Journal

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“…1969): the isoenzytne itbnormalities and inhibition of B-falactosidase activity could be reproduced iu rirro by addition of chondroitin sulfate to tissue homogenates (KIYT p f ul.. 1973). Also inhibitory action of GAG on brain sialidase has been reported (HEIJLMAN, 1974). Interference of the GAG on the ability of specific isoenzymes of /I-galactosidase, sialidase, reported (OCKERMAN & HUI.THlK(i.…”

Section: Discussionmentioning

confidence: 99%

“…Also the activity of lactosyl ceramide p-galactosidase in Hurler fibroblasts was normal (DAWSON, 1972). Moreover the inhibition of 8-galactosidase by GAG was completely cancelled out by chloride ions (Ho & FLUHARTY, 1975) and there are n o indications of diminished sialidase activity in MPS (HEIJLMAN, 1974).…”

Section: Discussionmentioning

confidence: 99%

Neurochemistry of the Mucopolysaccharidoses: Brain Lipids and Lysosomal Enzymes in Patients With Four Types of Mucopolysaccharidosis and in Normal Controls

Constantopoulos

Dekaban

1978

Journal of Neurochemistry

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Abstract— Lipids and certain lysosomal enzymes were measured in the cerebral gray and white matter and in the liver of unaffected controls and six patients with mucopolysaccharidosis (MPS). Three of the patients had MPS Type I (Hurler), one Type II (Hunter), one Type IIIA (Sanfilippo A) and one Type V (Scheie). The glycosaminoglycans (GAG) of those tissues have been fully characterized previously (Constantopouloset al., 1976). Results of the present study: the normally minor brain monosialogangliosides GM2 and GM3 were markedly increased in the gray and to a lesser extent in the white matter of all the patients, except the patient with MPS Type V. On an average GM2 comprised 8.2 and 6.3, and GM3 11.8 and 6.0% of the total ganglioside neuraminic acid of the gray and white matter respectively in all patients with MPS I, II, and IIIA (normal subjects had less than 1). Ceramide dihexoside was also increased in the gray matter of the patients with MPS I, MPS II and MPS IIIA. The sphingolipid abnormalities were found only in tissues containing excessive amounts of partially degraded dermatan and heparan sulfates or heparan sulfate alone. Of the six acid hydrolases assayed, the activity of /f‐glucosaminidase was increased in both brain and liver, while that of α‐galactosidase and β‐galactosidase was diminished, particularly in the liver. These results suggest that the partially degraded heparan sulfate (and perhaps the dermatan sulfate) which accumulate in the tissues of the patients with MPS may inhibit catabolic enzymes of various sphingolipids. In turn, accumulation of sphingolipids could be responsible at least for some of the brain damage and the mental retardation in MPS I, II and IIIA.

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Decreased ganglioside neuraminidase activity in fibroblasts from mucopolysaccharidosis patients Inhibition of the activity in vitro by sulfated glycosaminoglycans and other compounds

Baumkötter

Cantz

1983

Biochimica et Biophysica Acta (BBA) - General Subjects

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The Inhibitory Action of Glycosaminoglycans on Brain Sialidase

Cited by 4 publications

References 0 publications

Neuraminidase inhibition by chemically sulphated glycopeptides

Neuraminidase inhibition by chemically sulphated glycopeptides

Neurochemistry of the Mucopolysaccharidoses: Brain Lipids and Lysosomal Enzymes in Patients With Four Types of Mucopolysaccharidosis and in Normal Controls

Decreased ganglioside neuraminidase activity in fibroblasts from mucopolysaccharidosis patients Inhibition of the activity in vitro by sulfated glycosaminoglycans and other compounds

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