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REACTIVE OXYGEN SPECIES AND ELECTRON EXCITATION IN AQUEOUS SYSTEMS: TWO SIDES OF THE COIN.
V.L. Voeikov
Lomonosov Moscow State University, Russia, and International Institute of Biophysics, Neuss, Germany.
Alexander Gurwitsch was the first to consider and experimentally demonstrate the crucial role of oxygen and its reactive species in the emerging of mitogenetic radiation. According to him, oxidative reactions play also a central role in supplying a continuous influx of energy („pumping") for the formation and sustainment of highly non-equilibrium cytoplasmic „molecular constellations", which are the major store of free energy for the performing of all functions of living cells. He insisted that all these processes of energy generation and utilization need participation of oxygen compounds which are now known as „Reactive Oxygen Species" (ROS). However, Gurwitsch ideas and factual evidence passed without notice for most biochemists, biophysicists and physiologists of his time and are practically unknown now. On the other side, for many decades ROS were considered only as highly toxic by-products of „normal" oxidative metabolism, as the starters for deleterious chain reactions, in the course of which membranes, proteins, and nucleic acids are damaged.
This situation began to change only recently. More and more experimental evidence of beneficial role of ROS for the well-being of animals and humans is obtained. It turns out that without constant supply of ROS (though in a very small quantities) with air and water consumed by an organism, its vital functions gradually fade out. Studies in model systems, such as cell cultures has revealed the important bio-regulatory actions of ROS on many, if not all cellular functions. It also became clear that there are multiple non-enzymatic and very specific enzymatic mechanisms for constant as well as inducible ROS production. In particular, the enzyme NADPH-oxidase which produces superoxide radical anion, from which other ROS are later on generated, turned out to be ubiquitous. Some estimates show that plants may convert up to 80% of oxygen consumed into ROS, while animals convert to ROS not less than 10-15% and up to 30% of oxygen consumed by them. Thus there is a serious contradiction between traditional views upon ROS as only deleterious chemical species and factual evidence of a demand for them of all the living organisms and of their highly specific regulatory action upon vital processes. The latter is very difficult to explain basing on the dominating in current biochemistry concept of a „key – keyhole" action of regulatory substances, because most ROS have in fact very low chemical specificity in their reactions with a variety of organic molecules.
However, there is a certain specific feature of reactions with ROS participation, which is usually not taken into consideration in conventional biochemistry, but which may be very important for the understanding of their mode of functioning. Most ROS are free radicals or species which easily convert into free radicals. It is well known that in reactions with free radicals participation a lot of energy is released, and, in particular, in the reactions of radical recombination the products in electron excited states emerge. There is a lot of direct and circumstantial evidence that when such reactions proceed in aqueous systems this energy do not easily dissipate into heat, but it can be rather transferred to appropriate acceptors, and may be used as the energy of activation for triggering specific chemical and biochemical reactions, and even accumulated in highly polymeric molecules present in water, such as nucleic acids, proteins and their ensembles which may exist for a rather long time as specific non-equilibrium collectives due to the radiative and radiation-less energy transfer between their members. We present evidence, that even in the most primitive proto-biochemical aqueous systems, such as solutions of the simplest monosaccarides and amino acids oscillatory chemiluminescent processes with a highly organized temporal patterns of oscillations develop in the presence of oxygen there. It is plausible to suppose that when similar processes go in much higher organized environs of cells and intercellular matrix, where free radicals are produced enzymatically and where their recombination is catalyzed by specific enzymes and non-enzymatic "antioxidants" generation of electron excited species is much more spatio-temporaly ordered. We suggest that the mechanisms of biological action of ROS are determined by the structural patterns of the processes with ROS participation rather than by the average concentration of ROS in cells and tissues. By the "structural pattern of the process" we mean here the frequency-amplitude and phase relation patterns of electron excited states generation and their relaxation the course of ROS reactions with each other and other molecules. Energy released in these reactions is used, as mentioned, as an activation energy for the specific biochemical processes, for the continuous pumping of the non-equilibrium state of inter- and intracellular structural components, while the structural patterns of ROS reactions determine biochemical and physiological rhythmic modes.
Water plays a very special role in these processes. In particular, it has recently been demonstrated that ROS may appear in water due to its homolytic dissociation under the action upon water of such mild impetus as streaming, filtration, sonication, microwave irradiation, etc. From this it follows that ROS and free oxygen are constantly generated by natural water, and any living forms that are themselves consist mostly of water depend very much upon these species and the processes associated with their turnover. From a more broad perspective the processes with ROS participation in aqueous systems preceded and were the necessary condition for the emergence of organic living forms on Earth.
Our emphasis here on wholesome and bio-regulatory function of ROS does not rule out previous finding in which their harmful effects were observed. However, these effects were mostly documented the in vitro systems in which spatio-temporal organization of biochemical and biophysical properties characteristic for undamaged organisms is to more or less extent violated. Other data of toxic action of ROS were usually get in experiments where their excessive concentrations were applied, and when non-specific chain reactions of ROS with bio-molecules, rather than radical recombination reactions are already dominating.
To conclude, we suggest that the energetic side of the reactions with ROS participation: the processes of high energy quanta origination, transfer and utilization in living systems -- are much more important under the normal conditions of their existence and in their reactions upon physiological stimuli than non-specific chemical reactions of ROS in artificial conditions which are currently the major subject of investigation.
