Handbook of Vitamin C Research

214J.J.G. Marin, M.A. Serrano, M.J. Perez,et al.proteins in anti-oxidant systems responsible for cell homeostasis or more cell-specificroles in which vitamin C is involved, such as trans-epithelial transfer or collagensynthesis. Changes in the expression of these transporters in association with oxidativestress and inflammation have been described. In the present review, their role inphysiology and in both the aetiology and pathogenesis of several diseases is discussed.1. IntroductionAlthough the active form of vitamin C is ascorbic acid (AA), the oxidized formdehydroascorbic acid (DHA) is also useful, because once inside the cell DHA can bebiotransformed or recycled into AA by several enzymatic mechanisms. Owing to theimportance of vitamin C in cellular homeostasis, both AA and DHA are efficiently taken upby cells via plasma membrane transporters belonging to two different families of proteins ofsolute carriers (SLC2A and SLC23).An impaired expression and/or function of these transporters could be involved in severalsituations in which low levels of vitamin C in tissues have been found, regardless of normalor enhanced amounts of this compound in the diet. This occurs for instance in leucocytes inacute infections and several other pathological conditions (Basu & Schorah, 1982).Different unhealthy life habits, such as cigarette smoking, reduce vitamin C intake.However, even when this is maintained vitamin C deficiency may persist in tissues due toimpaired vitamin C uptake. Both events may lead vitamin C levels in the leucocytes ofsmokers to become reduced (Pelletier, 1975; Kallner et al., 1981; Schectman et al., 1989).The shared characteristic of many situations leading to reduced contents of vitamin C inserum and leucocytes, despite normal levels of intake, is the enhanced generation of oxygenreactive species, which involves an increased turnover of AA (Cochrane et al., 1983;Anderson et al., 1988; Frei et al., 1989). How these changes regulate the expression ofvitamin C transporters is as yet unknown. However, there is evidence, reviewed below, of theexistence of important relationships between vitamin C handling and several diseases thataffect many different organs.2. Synthesis and Metabolism of Vitamin CVitamin C is a carbohydrate compound related to glucose whose active form is AA. Thismolecule contains an ene-diol group that confers electron lability, which makes it able toparticipate in oxidation-reduction reactions through its electron donating and electronaccepting properties. Thus, AA is a strong reducing agent, and is the co-factor of reactionscatalyzed by Cu 2+ -dependent monooxigenases and Fe 2+ -dependent dioxygenases (Linster &Van Schaftingen, 2007). As a vitamin, AA and DHA are present in food components, mainlyfrom plant sources, at levels several orders of magnitude higher than most of other vitamins.This characteristic is because vitamin C is chemically related to monosaccharides, i.e.,compounds that are very abundant in plants (Linster & Van Schaftingen, 2007). Anothercharacteristic of vitamin C is that it cannot be considered as an actual vitamin for many