Handbook of Vitamin C Research

302Mustafa NazıroğluNO is synthesized during the enzymatic conversion of L- arginine to L- citrulline bynitric oxide synthase (NOS). With an unpaired electron, NO, which is a highly reactive freeradicals, damages proteins, carbohydrates, nucleotides and lipids and, together withinflammatory mediators, results in cell and tissue damage [12]. NO potentially relaxes arterialand venous smooth muscles and, less strongly, inhibits platelet aggregation and adhesion[13]. NO donors, acting as vasodilating agents, are therefore a possible therapeutic approach[14]. Reactive nitrogen species have been associated with asthma, ischemia/reperfusioninjury, septic shock and atherosclerosis via ion channel activation [10]. The two commonexamples of reactive oxygen species are NO and nitrogen dioxide [15]. NO is produced bythe enzyme NO synthase. There are 3 types of NOS: Neuronal NOS (nNOS) and endothelial(eNOS) are constitutive NOS synthases, and responsible for the continuous basal release ofNO. The iNOS is present in mononuclear phagocytes (monocytes and macrophages) andproduces a large amount of NO [13].Under circumstances that are not yet well understood, NO reacts with superoxide radical(O 2 .- ) to form peroxynitrite (ONOO) [15], a compound that, having a pKa of 6.8, can beprotonated at physiological pH to form peroxynitrous acid (ONOOH) [16]. Peroxynitrousacid is unstable, giving rise to a chemical species with hydroxyl radical (OH)-like reactivityand to nitrogen dioxide (NO 2 ), two free radicals that spontaneously degrade to the morestable nitrate (NO 3 ) [17,18]. In situ, peroxynitrite is formed by a NOS1- (or NOS2) catalyzedreaction when the concentrations of L-arginine are suboptimal and thus O 2 is produced by theenzyme [15, 17]. Peroxynitrite can be synthesized after persistent inhibition of mitochondrialrespiratory chain activity by NO [18].Oxidation proteins appear to play a causative role in many chronic diseases of agingincluding neurodegenerative diseases such as epilepsy and Alzheimer‘s disease. Frank andGupta [19] reviewed role of oxidative stress in neurodegenerative diseases as fellows; a) cellfrom old individuals are more susceptible to oxidative damage than cells from young donors;b) oxidative protein modification is not random; c) some of the damage can be prevented byantioxidant, but there is an age-dependent difference; and d) an age-related impairmentrecognition and destruction of modified proteins exist.Structure and Properties of Vitamin CVitamin C occurs in two forms, namely the reduced ascorbic acid and the oxidizeddehydroascorbic acid. Only the L isomer of ascorbic acid has activity. Although the majorityof the vitamin exists as ascorbic acid, both forms are biologically active. Ascorbate acts in theaqueous phase and it reduces superoxide and peroxyl radical. It exists as the enolate anion atphysiological pH. Dehydroascorbate formed by a second reduction or dismutation reactionand it recycled by dehydroascorbate reductases, a GSH dependent enzyme. Dehidroascorbylradical may also dismutase to ascorbate and dehydroascorbate [3].In foods, the reduced from of ascorbic acid may reversibly oxidize to the dehydro formwith dehydroascorbic acid further oxidized to the inactive the irreversible compound ofdiketogulonic acid. This change takes place readily, and thus ascorbic acid is very susceptiblethrough oxidation, a change that is accelerated by heat and light. Ascorbic acid is so readily