Handbook of Vitamin C Research

218J.J.G. Marin, M.A. Serrano, M.J. Perez,et al.3. Transport of Ascorbic Acid andDehydroascorbic AcidIn both species able to synthesize AA and in those that need to obtain the compoundfrom external sources, their cells use vitamin C to carry out vital functions. Accordingly, thiscompound must cross the plasma membrane to enter the cells. Owing to its size and polarity,simple diffusion of vitamin C (both AA and DHA) across the lipid bilayer is very poor (Rose,1987) and hence its uptake requires the participation of plasma membrane proteins thatmediate passive or active secondary transport systems (Wilson, 2005). The proteinresponsible for this process depends on whether the transported compound is in the reduced(AA) or oxidized (DHA) form.The cellular uptake of DHA is carried out by passive hexose transporters belonging tothe GLUT family (gene symbol SLC2A); more specifically, by the GLUT1, GLUT3 andGLUT4 isoforms (Figure 3). The driving force for this transport is supplied by the inwardlydirectedelectrochemical gradient of DHA (Figure 3). Once inside cells DHA is reduced toAA. This may occur through the activity of several enzymatic systems. This permitsintracellular DHA concentrations to be maintained low and hence favours uptake by passivetransport. This mechanism of DHA uptake has been described in several cell types, such asastrocytes, enterocytes and osteoblasts (Agus et al., 1997; Daskalopoulos et al., 2002).However, GLUT-mediated DHA uptake is particularly important in cells unable to carry outAA uptake, with a very active metabolism, such as neutrophils (Vera et al., 1998). Owing tothe role of vitamin C in collagen synthesis, osteogenesis, and bone remodelling, the uptake ofDHA via GLUT plays a key role in osteoblast homeostasis (Qutob et al., 1998). Moreover,the presence of GLUT in astrocytes has been suggested to be involved in enhanced vitamin Cuptake as a mechanism of defence against ischemia-induced oxidative stress in nervous tissue(Siushansian et al., 1997; Huang et al., 2001). Since DHA uptake depends on the inwardlydirectedconcentration gradient and because the serum concentration of DHA is generally low(approximately 2 µM) (Dhariwal et al., 1991), under normal conditions the overall GLUTmediatedDHA uptake is low (Spielholz et al., 1997).In contrast, the serum concentrations of AA are much higher, close to 60 µM (Dhariwalet al., 1991). This, and the fact that AA is efficiently taken up through sodium-dependentsecondary active transporters, supports the concept that vitamin C is mainly taken up by thelatter rather than through the former mechanism.The proteins responsible for this process belong to the family of nucleobase transporters(gene symbol SLC23). The main AA transporters are the sodium-dependent carriers SVCT1(SLC23A1) and SVCT2 (SLC23A2). Thus, thanks to the energy of the inwardly-directedsodium gradient maintained by Na + /K + -ATPase activity, AA uptake may occur even againstan electrochemical gradient, with a Na + /AA stoichiometry of 2:1 (Figure 3). Both isoforms ofSVCTs differ in their kinetic characteristics, as will be commented below. These differences,together with their tissue-specific distribution, suggest a dissimilar role for these isoforms.Accordingly, SVCT1 may be involved in maintaining the general homeostasis of AA bydetermining intestinal absorption and renal elimination of this vitamin, whereas SVCT2,which is particularly highly expressed in metabolically active cells, may be involved in theprotection of these cells against oxidative stress.