- Lithium lacks known biological roles yet is used clinically as ionic therapy for bipolar and other psychiatric disorders; its molecular mechanism remains unclear.
- Non-specific surface binding to macromolecules cannot explain therapeutic effects at relevant concentrations.
- Quantum mechanical calculations show Li+ preferentially binds PIP2, alanine glyoxylate aminotransferase 2 enzyme and glycogen synthase kinase 3, implying binding may explain activity and toxicity.
Phys Chem Chem Phys. 2026 Sep 22. doi: 10.1039/d6cp03114e. Online ahead of print.
ABSTRACT
Lithium does not have any known roles in biology, but is nevertheless used as medicine for bipolar and other psychiatric disorders in its ionic form. The mechanism of action of lithium as a drug is not yet fully established. Although lithium preferentially binds to the surface of biological macromolecules, such non-specific interactions cannot explain the ion’s therapeutic effect at relevant concentrations. Here, a computational, quantum-mechanical based approach was used to estimate lithium’s affinity to several potential targets. These include the second messenger PIP2, the alanine-glyoxylate aminotransferase 2 enzyme (found by analogy to a bacterial Li+-binding protein), and glycogen synthase kinase-3. The results show preferential binding of Li+ to the examined protein targets, which might explain the ion’s activity and toxicity.
PMID:42770460 | DOI:10.1039/d6cp03114e
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