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What is Oxidation?
Combination of substrate with oxygen. Reaction in which the atoms in a compound lose electrons. Any compound, including oxygen, that can accept electrons is an oxidant or oxidizing agent (pro-oxidant), while a substance that donates electrons is a reductant or reducing agent (antioxidant).
Particals, which are not free radicals hydrogen peroxide, H2O2 (Fentons reaction) hypochlorous acid, HClO ozone, O3 singlet oxygen, 1O2
Superoxid dismutase
(EC 1.15.1.1, SOD) 2O2. - + 2H+ H2O2 + O2 SOD - is present in all oxygen-metabolizing cells, different cofactors (metals) an inducible in case of superoxide overproduction
Superoxid dismutase
Mn 2+ SOD (SOD1)
Superoxid dismutase
Cu 2+/Zn 2+ SOD (SOD 2) dimer, Cu = redox centr cytosol, intermitochondrial space hepatocyt, brain, erytrocyte high stability, catalysation at pH 4,5-9,5
Glutathion peroxidases
elimination of intracellular hydroperoxides and H2O2 2 GSH + ROOH GSSH + H2O + ROH cytosolic GSH - glutathionperoxidasa (EC 1.11.1.9, cGPx) extracelullar GSH - glutathionperoxidasa (eGSHPx) phospholipidhydroperoxide GSH peroxidase (EC 1.11.1.12, PHGPx)
Catalase
(EC 1.11.1.6, KAT) 2 H2O2 2 H2O + O2 high affinity to H2O2 : peroxisomes hepatocytes mitochondria, cytoplasm of erytrocytes tetramer with Fe, needs NADPH
Low-molecule endogennous antioxidats III glutathione (GSH, GSSG) in all mammalian cells (1-10 mmol/l) important redox buffer 2 GSH GSSG + 2e- + 2H+ ROS elimination, stabilisation in reduction form ( SH- groups, tocopheryl and ascorbate regeneration) substrate of glutathione peroxidases
Oxidative stress
Equilibrium failure between creation and a elimination of RONS leads to
oxidative stress
Be carefull - this equilibrium can be disbalance in both sides
Damage
unsaturated bonds loss arising of reactive metabolites (aldehydes) changes in fluidity and permeability of membranes membranes integral enzymes are influenced
Damage
agregation, fragmentation and cleveage reaction with hem iron ion functional group modification changes in: enzymes activity, ions transport proteolysis
saccharide ring cleveage mutation bases modification translation mistakes chain breakeage protoesynthesis inhibition
Antioxidants determination
ascorbate tocopheryl
SOD GSHPx
glutathion
Professor Mike Clifford, from the University of Surrey. While a comprehensive body of data has been gathered on the in vitro antioxidant activity of polyphenols, phenols and tannins, less has been discovered in vivo, and one of the greatest challenges is to understand how the body processes these chemicals, as well as copes with their metabolites. Phenolics undergo several metabolising steps in the body, including glucuronidation, methylation, sulphatation and dehydroxylation. All these reactions affect their overall antioxidant activity, and therefore potentially modulate their protective effect. One of the main challenges for nutritional research in the years to come will be to identify the compounds responsible for the protective effects in vivo (Professor Crozier).
The antioxidant activity of dietary nutrients is also susceptible to its environment, the presence of proteins and other antioxidants. Certain polyphenols may readily pass the gastrointestinal barrier (e.g. caffeic acid) while other are poorly absorbed (e.g. rutin). This makes it very difficult to correlate the antioxidant capacity of a compound in vitro with its effect in vivo. Moreover, the composition of a meal affects the absorption and subsequent bioavailability of each polyphenol. What is known as the food matrix effect is currently being studied by Mullen, who adds that comparing the bioavailability of the antioxidants in dark chocolate when eaten with and without milk revealed lower levels of antioxidants in the plasma when the dark chocolate was eaten with milk , while cream delayed the absorption of phenolics from strawberries but also warns that this observation does not provide a complete answer to the problem, as many of the dietary antioxidants studied are rapidly metabolised and difficult to identify and quantify once absorbed. The role of these metabolites may be crucial. However little is known about them or their mode of action, which is potentially independent of their antioxidant activity.
The behaviour of a compound during its journey through the gastrointestinal tract is crucial in order to understand its impact on systemic health. Following ingestion of a polyphenol-rich meal, the plasma antioxidant capacity is enriched, suggesting that the antioxidant compounds may pass the blood barrier, reduce the oxidant pool derived from the meal (mainly iron) or spare the bodys antioxidant defences. Professor Clifford, who has a special interest in the absorption and metabolism of phenols, polyphenols and tannins (PPT), emphasises that PPT metabolites only occur in the plasma in trace amounts, even after massive doses, and will be barely detectable after one normal portion of fruit and vegetables (as defined in five-a-day): The antioxidant effect in the tissues associated with these mammalian metabolites is negligible and unlikely to be health-promoting by such a mechanism. They do not accumulate following repeat doses as all the metabolism is designed to make them easily removed from the body. The native polyphenols can be powerful antioxidants, but normally they do not occur in the plasma and tissues. If they did, and especially if they accumulated (as when given intravenously), they would be dangerous because they can generate free radicals through redox cycling. This is why the body has developed such good defences against them.
With such a vast degree of variation between the powerful, native dietary antioxidants tested in vitro, and their watered-down version occurring in vivo, it is difficult to establish a direct link between the antioxidant capacity of a molecule and its health-promoting effects. As Mullen points out, the requirement for ascorbate to prevent scurvy is independent from its antioxidant activity, as vitamin C is required for its role in collagen production. This point of view is shared by Professor Clifford, who highlights that dietary polyphenols are also likely to be beneficial through alternative routes, including their ability to delay glucose absorption from the duodenum, potentially protecting against the development of type-2 diabetes, or their prebiotic effect on the gut microflora and limitation of neurotoxin producing micro-organisms.
Thus, it is clear that the science underlying the recommended 5 portions of fruit and vegetables per day is more complex than thought when species, metabolism, environment and human factors are taken into consideration. We may therefore be able to refine this advice in the future but, in the meantime, the public will do well to heed the current basic recommendation for their health and well-being, bearing in mind that, in order to secure a wide range of antioxidants, 35 portions a week covering a wide variety of fruit and vegetables are better than the same five everyday.