A Molecular Model for Lithium's Bioactive Form.

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TitleA Molecular Model for Lithium's Bioactive Form.
Publication TypeJournal Article
Year of Publication2016
AuthorsBriggs, KT, Giulian, GG, Li, G, P Y Kao, J, Marino, JP
JournalBiophys J
Volume111
Issue2
Pagination294-300
Date Published2016 Jul 26
ISSN1542-0086
Abstract

Lithium carbonate, a drug for the treatment of bipolar disorder, provides mood stability to mitigate recurrent episodes of mania and/or depression. Despite its long-term and widespread use, the mechanism by which lithium acts to elicit these psychological changes has remained unknown. Using nuclear magnetic resonance (NMR) methods, in this study we characterized the association of lithium with adenosine triphosphate (ATP) and identified a bimetallic (Mg·Li) ATP complex. Lithium's affinity to form this complex was found to be relatively high (Kd ∼1.6 mM) compared with other monovalent cations and relevant, considering lithium dosing and physiological concentrations of Mg(2+) and ATP. The ATP·Mg·Li complex reveals, for the first time, to the best of our knowledge, that lithium can associate with magnesium-bound phosphate sites and then act to modulate purine receptor activity in neuronal cells, suggesting a molecular mode for in vivo lithium action.

DOI10.1016/j.bpj.2016.06.015
Alternate JournalBiophys. J.
PubMed ID27463132