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On the true role of oxygen free radicals in the living state, aging, and degenerative disorders.

Oxyradicals are generally considered harmful byproducts of oxidative metabolism, causing molecular damage in living systems. They are implicated in various processes such as mutagenesis, aging, and series of pathological events. Although all this may be justified, evidence is accumulating that it is an oversimplified view of the real situation. We can assume nowadays that the living state of cells and organisms implicitly requires the production of oxyradicals. This idea is supported by experimental facts and arguments as follows. (1) Complete inhibition of the oxyradical production by KCN (or by any block of respiration) kills the living organisms much before the energy reserves would be exhausted. (2) Construction of the supramolecular organization of the cells (especially of their membranous compounds) requires the cross-linking effect of oxyradicals, particularly that of OH* radicals. (3) Blast type cells produce much fewer oxyradicals than do differentiated ones, and interventions increasing the production of OH* radicals induce differentiation of various lines of leukemic (HL-60 and K562) and normal (fibroblasts, chondroblasts, etc.) cells, while SOD expression increases greatly. (4) It is reasonable to assume that the continuous flux of OH* radicals is prerequisite to maintenance of constant electron delocalization on the proteins, which is a semiconductive phenomenon suggested in 1941 by Szent-Györgyi, but it has never been proven experimentally. It is theoretically possible to describe the function of the synapses as that of a single p-n-p transistor, assuming that the free radical flux maintains electron movements on the subsynaptic structures, while the actual membrane potential is governing the electron flux. This theoretical approach may open completely new possibilities for our understanding of the normal functions of living organisms, such as basic memory mechanisms in brain cells, their aging processes, and therapeutic approaches to many degenerative disorders, such as various types of dementia.