Effect of neurotoxic divalent cations on the activity of the intrinsic nerve ending membrane-associated sialidase of bovine brain.

Abstract:

:Exposure to Hg2+ below 10 micrometer destroys synaptosomal membrane-associated sialidase of bovine brain in situ. Inhibition by Cu2+ occurs only at relatively higher concentrations, and is demonstrable after the synaptosomal membrane preparation has been presaturated with Cu2+ . Pb2+ does not inhibit enzymatic activity. Hg2+ does not exert a significant effect on the free energy of association of monomeric brain gangliosides into aggregates, or on the stability of the aggregate forms, as estimated by ultracentrifugal analysis of the ion-independent moment of ganglioside micelles as a function of concentration. Hg2+ inhibits synaptic membrane sialidase acting both in situ on the native sialocompounds in the membrane, or on exogenous ganglioside. Kinetic analyses of the exogenous activity in membranes exposed to Hg2+ reveal lowered Vmax values but no substantial change in Km for synaptosomal membrane gangliosides. These findings suggest that the powerful inhibitory effect exerted by Hg2+ on nerve ending membrane sialidase is enzyme directed, not substrate directed. It may be postulated that part of the neurotoxic effect of low levels of Hg2+ stems from an interference with synaptic metabolism by the destruction of membrane-associated sialidase. This enzyme can serve the purpose of modulation of synaptic negative charge density by releasing bound, strongly anionic, sialic acid from highly concentrated sialocompounds in the membrane.

journal_name

Neurochem Res

journal_title

Neurochemical research

authors

Yohe HC,Rosenberg A

doi

10.1007/BF00964363

subject

Has Abstract

pub_date

1978-02-01 00:00:00

pages

101-13

issue

1

eissn

0364-3190

issn

1573-6903

journal_volume

3

pub_type

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