C holestery I -13- hydrox y-octa-c9,111-diene o-c
C holestery I -13- hydrox y-octa-c9,111-diene
Figure "J.2 Oxidative damage to poiyuns.it urn led lipids tends to spread
Mela! ion chelation: The formation of ROS is effectively reduced by maintaining iron and copper in tightly bound form that cannot participate in Fen ton-type reactions. The metal-chclating capacity of some food-derived compounds, such as Havonoids, may provide additional protection. The relevance of this effect at the cellular level remains unclear, however.
Enzyme-catalyzed reactions: The body has an elaborate system to protect against ROS. These systems tend to be most active at the sites of greatest ROS release, Catalase (ECU 1.1 ,ii>. which contains both heme and manganese, dissipates hydrogen peroxide in peroxisomes to oxy gen and water. This enzyme w ith its high capacity and low affinity is best suited to detoxify overflow quantities and sudden bursts of hydrogen peroxide. Other enzymes with peroxidase activity have lower capacity, but their high substrate affinity keeps hydrogen peroxide concentrations very low . This group of high affinity peroxidases includes the peroxiredoxins(Prx), which arc closely related heme enzymes.
Different superoxide dismutase (EC22.214.171.124 ) isoenzymes in cytosol and the extracellular space convert superoxide radicals to hydrogen peroxide (reaction equation 4). AH isoenzymes contain copper and a second transition metal. The isoenzyme in mitochondria contains manganese, the ones in cytosol and extracellular fluids contain zinc or iron.
Another high-capacity free radical scavenger in extracellular fluid is the copper-enzyme ferroxidase (ceruloplasmin, iron ( 11 ):oxygen oxidoreductase. EC1.I6..1,1 ).
Thioredoxin reductase (EC 126.96.36.199) is a ubiquitous NADPH-dependent selenoen/yme in cytosol that reduces both dehydroascorbate and the scm¡deitydroascorbate radical to ascorbate (May et al1998).
A different protective strategy seeks to remedy the damage. Four different selenium-containing glutathione peroxidases (EC1. 11.1.9) with distinct tissue distributions and activity profiles use glutathione (GSH) for the reduction of peroxides of free fatty acids and other lipids. Another example is the activity of arylestemse (paraoxonase I, PONI. EC188.8.131.52) in high-density lipoprotein (HDL). This enzyme cleaves the fatty aldehydes from damaged phospholipids and releases them Irom the lipoprotein particle for further metabolic treatment in the liver and other tissues (Ahmed et al., 200! ). Antioxidants: The body uses both fat-soluble and water-soluble compounds to reach all cellular compartments.
Tibi« 9.2 Anuokidaot enzymes
Catalase (EC1.I1.5.6. heme)
Superoxide dismutase (EC 1,15.1.1, iron, manganese, zinc) Peroxidase (EC 184.108.40.206. heme) Glutathione peroxidases (EC!, 11.1.9, selenium) Thioredoxin reductase (EC220.127.116.11, selenium)
Arylcsteraw (EC3 1,1.2)
Tm r,i hydro b iopt rrrn Unr acid
Conjugal ttil lino Ira' acid
Tm r,i hydro b iopt rrrn Unr acid
Conjugal ttil lino Ira' acid
The essential nutrient ascorbate is a particularly versatile antioxidant, because it can quench radicals that have one or two excess electrons. The systems for the regeneration of the oxidized forms include NADH-dependent monodehydroaseorbate reductase (EC18.104.22.168), thioredoxin reductase (ECL6.4.5). and an NADH-dependent dehydroascorbate-reducing transporter in erythrocytes (May et al.. ILWK) Thioredoxin is a small peptide with two redox-active cysteines that potently quenches singlet oxygen and hydroxy I radicals. The oxidation of its cysteines reduces oxidants or oxidized compounds. It also detoxifies hydrogen peroxide in conjunction with a group of enzymes, the peroxiredoxins. Thioredoxin reductase (EC22.214.171.124) uses NADU to rapidly regenerate the oxidized thioredoxin. Lipoate, tetrahydrobiopterin, uric acid phenols, flavonoids ami isollavones, additional protein disulfides, and possibly melatonin add to the mix of water-soluble antioxidants.
Vitamin 1- is particularly important for antioxidant protection in lipoproteins, membranes, and other lipophilic environments Since ihe interaction of R< )S with vitamin E generates the tocopheroxyl radical, the net effectiveness depends on adequate availability of ascorbate and other co-antioxidants for regeneration (Terentis el al.. 2002). Ubiquinone, and tetrahydrobiopterin. have considerable antioxidant potential unrelated to their function as enzyme cofactors. In addition to these endogenous metabolites, a wide range of food-derived compounds is known to provide additional protection. Hundreds of carotenoids from fruits and vegetables increase the resistance of tissues to the harmful effects of ROS.
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Whenever a doctor informs the parents that their child is suffering with Autism, the first & foremost question that is thrown over him is - How did it happen? How did my child get this disease? Well, there is no definite answer to what are the exact causes of Autism.