Effect of neurotoxic divalent cations on the activity of the intrinsic nerve ending membrane-associated sialidase of bovine brain.
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.
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002413:Cations, Divalent / Q000494:pharmacology*; D002417:Cattle; D003300:Copper / Q000494:pharmacology; D005732:Gangliosides / Q000378:metabolism; D007700:Kinetics; D007854:Lead / Q000494:pharmacology; D008628:Mercury / Q000494:pharmacology; D008823:Micelles; D009439:Neuraminidase / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D013570:Synaptic Membranes / Q000201:enzymology*
D002413:Cations, Divalent; D005732:Gangliosides; D008823:Micelles; D007854:Lead; D003300:Copper; D009532:Nickel; D009439:Neuraminidase; D008628:Mercury