Simplifying the complexity of cell signaling in medicine and the life sciences: radicals and electrochemistry.

There have been various comments on the complexity of cell signaling and the need for simplification. Recently, new mechanics was proposed by Hlavacek and Faeder as a means of achieving this goal. Some of the important tenets include: (1) phosphorylation of nearby phosphorylation sites is likely to be cooperative and (2) many phosphorylation sites regulate the binding activities of protein interaction domains. Also, phosphorylation sites within a protein can be lumped together into a single effective domain. Recently, reports have appeared that provide a simplified base for cell signaling involving electrochemistry (electrostatics and electron transfer) and radical species. In the electrostatic approach, a vital role is played by anions of phosphate and sulfate, as well as cations of metals and bioactive organic cations, such as acetylcholine, GABA and amino acid zwitterions, in addition to protein ions. The theoretical base can also be applied to receptor-ligand chemistry. The hypothetical framework can complement the new mechanics approach by providing an underlying rationale based on electrochemistry and radicals.