Ascorbic Acid. Ascorbic acid (L-threo-hex-2-enomo-1,4-lactone), also known as Vitamin C was isolated and identified in 1928 by a Nobel laureate, Professor Xxxxxx Xxxxx-Xxxxxxx, a discovery which led to improved nutrition in the 20th Century [85]. Vitamin C deficiency can famously cause scurvy, but is also associated with defective connective tissue and wound healing [86]. It is a diacid and exisits almost exclusively as the monoanion (ascorbate) at physiological pH range (pk1=4.2, pK2= 11.8) [87]. The conjugated structure of the five-membered lactone ring, offers stabilization of monodehydroascorbate, that is, the free radical one-electron oxidation product by delocalization of the unpaired electron [87]. It is a chain breaking antioxidant that can readily scavenge peroxynitrite, nitrogen dioxide radical, hypochlorous acid, superoxide anions and hydroperoxyl radical [88]. It can also reduce antioxidant radicals back to their reduced form such as Vitamin E, as well as reduced glutathione and urate upon O3 or NO2 exposure [89-91]. Oddly enough, the reaction of ascorbate with transition metals can lead to the formation of deleterious products such as hydrogen peroxide that can lead to increased oxidation as can be expected from Xxxxxx chemistry [92]. However, it is a matter of great controversy as to whether this could occur in vivo [92]. Ascorbate is reversibly oxidised with the loss of one electron and forms the semidehydroascorbate radical, which is relatively unreactive due to its unpaired electron being in the delocalised n-system, further oxidation results in dehydroascorbate (DHA) which can be back reduced to ascorbate [93]. The ascorbyl radical will either disproportionate to generate ascorbate and DHA or it will be reduced to ascorbate by NADH-dependent semihydroascorbate reductase or it will be rapidly and irreversibly hydrolysed and thus depleted [93]. However, the mechanism of ascorbate transport in humans in general and the respiratory tract in particular are still under investigation. New ascorbate concentrations can only be acquired through the diet and are thought to be transported to the cerebrospinal fluid and blood stream via the Sodium Dependent Vitamin C Transporters
