Handbook of Vitamin C Research

154Borut Poljsak and John G. Ionescutumours. In this paper possible pro- and antioxidant effects of vitamin C will bepresented and their impact on human health will be discussed.1. IntroductionNatural antioxidants are generally considered to be beneficial fruit and vegetable components.Vitamin C is present in almost all foods of plant origin. It is an essential micronutrient inman, due to the absence of L-gulonolactone oxidase. Vitamin C has several important rolesand there are many enzymes utilizing ascorbate as a co-factor. The term vitamin C refers toboth ascorbic acid (AA) and dehydroascorbic acid (DHA), since both exhibit anti-scorbuticactivity. Ascorbic acid, the functional and primary in vivo form of the vitamin, is the enolicform of an α-ketolactone (2,3-didehydr L -threo-hexano-1,4-lactone). The two enolichydrogen atoms give the compound its acidic character and provide electrons for its functionas a reductant and antioxidant. Its one-electron oxidation product, the ascorbyl radical,readily dismutates to ascorbate and DHA, the two-electron oxidation products. Both theascorbyl radical and DHA are readily reduced back to ascorbic acid in vivo. Because of itsability to donate electrons, ascorbic acid is an effective antioxidant. The vitamin readilyscavenges reactive oxygen species (ROS) and reactive nitrogen species (RNS) (e.g.,hydroxyl, superoxide, singlet oxygen, and peroxynitrite, nitroxide radicals, respectively) aswell as peroxyl and hypochlorite (Frei et al., 1989; Halliwell and Whiteman 1997). The oneandtwo-electron oxidation products of ascorbate are relatively nontoxic and easilyregenerated by the ubiquitous reductants glutathione and NADH or NADPH . Both the oneandthe two-electron oxidation products of the vitamin are readily regenerated in vivo—chemically and enzymatically—by reduced glutathione, nicotinamide adenine dinucleotide(NADH), and nicotinamide adenine dinucleotide phosphate (NADPH ) dependent reductases(May et al. 1998; Park and Levine 1996). In addition to scavenging reactive oxygen speciesand reactive nitrogen species, vitamin C can regenerate other small molecule antioxidants,such as -tocopherol, glutathione (GSH), urate, and β-carotene, from their respective radicalspecies (Halliwell 1996). Many cells possess enzymes that can convert dehydroascorbate orascorbate radical back to ascorbate at the expense of GSH or NADH. Glutathione dependentdehydroascorbate reductase enzymes have been identified in plants and in severalmammalian tissues. Evidence that GSH and ascorbate interact in vivo is provided by studieson animals treated with the inhibitors of GSH synthesis (Halliwell and Gutteridge 1999).Severe glutathione depletion in newborn rats is lethal, but death can be prevented by highdoses of ascorbate (but not DHA).2. The In Vitro Evidence for an AntioxidativeRole of Vitamin CAt physiological concentrations, vitamin C is a potent free radical scavenger in theplasma, protecting cells against oxidative damage caused by ROS (Carr and Frei 1999). The