Alkali Metals

The most important biological role of sodium and potassium is to stabilize cell membranes and enzymes by electrostatic effects and osmosis. Besides, these ions transmit electrical signals by diffusion through a certain concentration gradient.

Crown ethers (Figure 10.5) form stable complexes with alkali metals and their biological importance is binding heteroatoms on the inside of the macromolecule while the surface is more lipophilic. As a result, pharmacologically active natural products of this kind function as antibiotics since they may transfer alkali metals in and out of the cells and thereby perturb the natural metal ion balance. The examples include valinomycin (Figure 10.6) and nonactin. Another efficient method for controlled cation transport through lipid double layers involves incorporation of ionic channels in membranes.

Lithium salts play a particular role in treatment of manic-depressive psychosis. The effective plasma concentration is 1 mM while 2 mM exhibits toxic side effects, and already 3 mM is a lethal dose. The Li+ ion has approximately the same radius as the Mg2+ ion, and both metal ions demonstrate high affinity phosphate binding. Lithium ions inhibit the enzymatic function of inositol monophosphatase thereby preventing release of phosphate from the active site. Inositol phosphatases are magnesium-dependent, and structural studies have shown that Li+ may bind to one of the catalytic Mg(II) sites. Inositol phosphates are responsible for mobilizing calcium ions, and Li+ will therefore influence the calcium ion level in cells, which makes it imperative to monitor the calcium concentration carefully in the patients during lithium treatment.

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