Calcium ions alter monoamine oxidase A activity

Rona R. Ramsay, Stephanie Armstrong

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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Abstract

Activation of the flavoprotein monoamine oxidase A (MAO A) by calcium ions has been reported in isolated mitochondria, in cell lines, and in vivo. Enhanced MAO A activity has been associated with a rise in oxidative damage (1,2), and with apoptosis in a neuronal cell line (5). Here, purified human MAO A and membrane-bound MAO A and B were used to investigate the direct regulation of MAO activity by Ca2+ ions.
At fixed substrate concentration the activity of purified MAO A was stimulated (<20%) by Ca2+ over a physiological range, a much smaller effect than observed in cells; Mg2+ and Mn2+ had no effect. However, when chelating agents (EDTA or EGTA) were added to remove divalent ions present in the water, MAO A activity was increased, but addition of 1 mM Ca2+ to the chelating buffer resulted in inhibition of activity requiring 10 min to reach the minimum. When assayed in HEPES buffer (50 mM, pH 7.4) without chelator, Ca2+ caused mixed-type inhibition of kynuramine oxidation with a Ki of 0.3 mM for binding to free enzyme. We conclude that Ca2+ (but not Mg2+ or Mn2+) interacts directly with purified MAO A to change the kinetic parameters resulting in decreased activity. In contrast, with membrane-bound MAO A (but not membrane-bound MAO B), Ca2+ enhances activity by doubling the Vmax without a change in KM. Recently, molecular dynamics simulations suggested that membrane attachment altered the conformational dynamics of MAO A and facilitated the opening of the substrate tunnel. The data here are consistent with a conformational change induced by Ca2+, the effect of which is different when the enzyme is stabilised in the membrane.
Original languageEnglish
Title of host publicationFlavins and Flavoproteins 2011
Subtitle of host publicationProceedings of the 17th International Symposium IUBMB S13/2011
EditorsSusan Miller, Russ Hille, Bruce Palfrey
PublisherLulu
Number of pages5
ISBN (Print)978-1-300-78640-5, 130078640X
Publication statusPublished - 2013
Event17th Intl Symposium on Flavins and Flavoproteins - Berkeley, CA, United States
Duration: 24 Jul 201129 Jul 2011

Publication series

NameFlavins and Flavoproteins

Conference

Conference17th Intl Symposium on Flavins and Flavoproteins
Country/TerritoryUnited States
CityBerkeley, CA
Period24/07/1129/07/11

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