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L’Accademia del Fitness

FROM NUTRITIONAL INTEGRATION TO PHYSIOLOGICAL MODULATION: THE ROLE OF GAS MEDIATORS. The correct functioning of all vital processes is modulated by the action of a number of gases, oxygen in primis. This element, under its molecular form (O2), by accepting the couples of reducing equivalents extracted in the course of terminal metabolism by a series of substrates, allows ATP synthesis which is necessary in all our biological functions. Moreover, by accepting single reducing equivalents, it generates specific reactive species (reactive oxygen species, ROS), such as superoxide anion (O2Ÿ), hydroxyl radical (HOŸ) and hydrogen peroxide (H2O2) which, in low amounts, modulate fundamental activities (i.e. cellular signal transduction, defence against bacteria) but, in high amounts, owing to their tendency to reach a stable configuration (electron pairs in all the orbitals), can subtract electrons from key molecules (i.e. nucleic acids), oxidising them and therefore altering their functions. In order to keep the high ROS production under control, and consequently their undesired effects, living organisms have developed a complex defence system made up of the various endogenous antioxidants (i.e. superoxide dismutase, peroxidase, catalase, albumin, bilirubin, uric acid, etc.) and exogenous antioxidants (ascorbic acid, tocopherols, carotenes, polyphenols, etc.). The absence of a physiological oxidant/antioxidant balance determines the so-called oxidative stress (OS), an emerging risk factor for our health which is associated not only to precocious aging but also to a high number of diseases (over 100), among which the most common and invalidating are for instance cardiovascular pathologies, neurodegenerative diseases, metabolic syndrome, obesity, diabetes, cancer etc. Unfortunately, OS does not give place to any clinical manifestation. Therefore, it can be diagnosed, in the presence of grounded suspects, only by means of specific laboratory exams (available today on blood, urine, exhaled breath etc.) (1). On the basis of such tests it is possible to identify subjects at risk,

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submit them to preventive personalised therapeutic strategies and monitor their efficacy over time, avoiding undesired effects of many integrators which are too often unnecessarily taken at present. The spreading of knowledge on oxygen, considered not only as hydrogen acceptor for energy production, but as the origin of reactive species which can modulate biological functions, has opened the way in the last thirty years to studies on other gases considered in the past inert or even toxic, such as ozone (O3), carbon monoxide (CO), carbon dioxide (CO2), nitric oxide (NO), sulphuric acid (H2S) and, very recently, molecular hydrogen (H2). Among these, molecular oxygen is produced exclusively through photosynthesis. The ozone derives from molecular oxygen, owing to the effect of electric discharges. Carbon monoxide is generated by heme thanks to the heme oxygenase enzyme. Carbon dioxide is released, spontaneously or enzymatically, by decarboxylation processes of β-keto acids. Nitric oxide is produced by the amino acid arginine through the catalytic action of nitric oxide synthase. The sulphuric acid is synthesized in the process of cysteine metabolism through cistathionine-β-synthase, cistathionine-γ-lyase and mercaptopyruvate sulfotransferase. The endogenous production mechanisms, if they exist, of molecular hydrogen are less clear. More and more studies show that all these “biogases”, thanks to their particular physical-chemical properties, by spreading more or less rapidly from the production site in the surrounding microenvironment, specifically tie themselves to determined molecular “receptive” targets, acting as real pleiotropic biochemical mediators (autocrine and/or paracrine) which can control vital biological functions such as vascular tone, stress response, apoptosis etc. (fig. 1) (2). For instance, if endogenously produced, nitric oxide - which had been considered an envi-

N. 10 - July 2013  

Wellness & Antiaging magazine

N. 10 - July 2013  

Wellness & Antiaging magazine