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A New Molecular Model for Lithium's Biological Interactions



John Marino, Katharine T. Briggs, Gary G. Giulian, Joe Kao, Gong Li


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, here 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 compared to other monovalent cations (Kd 1 mM) and relevant, considering lithium dosing and physiological concentrations of Mg2+ and ATP. The ATP·Mg·Li complex reveals, for the first time, that lithium can associate with magnesium-bound phosphate sites and then act to modulate purine receptor activity in neuronal cells, suggesting a new molecular mode for in vivo lithium action.
Biophysical Journal


lithium, NMR, relaxation, ATP nucleotide, magnesium, purine receptor


Marino, J. , Briggs, K. , Giulian, G. , Kao, J. and Li, G. (2016), A New Molecular Model for Lithium's Biological Interactions, Biophysical Journal, [online], (Accessed June 23, 2024)


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Created July 25, 2016, Updated October 13, 2022