Neurochemical Research

, Volume 3, Issue 1, pp 101–113 | Cite as

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

  • Herbert C. Yohe
  • Abraham Rosenberg
Original Articles

Abstract

Exposure to Hg2+ below 10 μM 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 nembrane 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 loweredVmax values but no substantial change inK m 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.

Keywords

Charge Density Sialic Acid Free Energy Divalent Cation Aggregate Form 

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Copyright information

© Plenum Publishing Corporation 1978

Authors and Affiliations

  • Herbert C. Yohe
    • 1
  • Abraham Rosenberg
    • 1
  1. 1.Department of Biological Chemistry The M. S. Hershey Medical CenterThe Pennsylvania State UniversityHershey

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