Dehydroascorbic acid transport

Vera JC, Reyes AM, Carcamo JG, Velasquez FV, Rivas Cl, Zhang RH, Strobel P, Iribarren R, Scher HI, Slebe JC, et al. 1996. Genistein is a natural inhibitor of hexose and dehydroascorbic acid transport through the glucose transporter, GLUT1. J Biol... 

Stahl, R. L., Farber, C. M., Liebes, L. F., and Silber, R., 1985a, Relationship of dehydroascorbic acid transport to cell lineage in lymphocytes from normal subjects and patients with chronic lymphocytic leukemia. Cancer Res. 45 6507-6512. 

Dehydroascorbic acid transport by GLUT4 in Xenopus oocytes and isolated rat adipocytes. J. Biol. Chem. 275 28246-28253. 

Absorption, Transport, and Excretion. The vitamin is absorbed through the mouth, the stomach, and predominantly through the distal portion of the small intestine, and hence, penetrates into the bloodstream. Ascorbic acid is widely distributed to the cells of the body and is mainly present in the white blood cells (leukocytes). The ascorbic acid concentration in these cells is about 150 times its concentration in the plasma (150,151). Dehydroascorbic acid is the main form in the red blood cells (erythrocytes). White blood cells are involved in the destmction of bacteria. 

Blood-to-retina influx transport GLUT1 D-Glucose/Dehydroascorbic acid + TR-iBRB Isolated retinal capillary [5, 13, 14, 43, 47]... 

GSH synthesis. GLUT1 transports dehydroascorbic acid, an oxidized form of vitamin C, to supply the retina with ascorbic acid [47],... 

Rose, R. C, Choi, J.-L., and Koch, M. J, (1988), Intestinal transport and metabolism of oxidized ascorbic acid (dehydroascorbic acid). Am. ]. Phifiloi, 254, OS24r-C828. 

The oxidative product of ascorbic acid, dehydroascorbic acid, is the preferred form of the vitamin for uptake by neutrophils, erythrocytes, and lymphocytes (27). Once within the erythrocyte, dehydroascorbic acid is reduced to ascorbic acid by a glutathione-dependent, dehydro-ascorbic-acid-reducing enzyme (20,28). However, the reduced form of ascorbic acid is found in most other tissues, that is, liver, lungs, kidneys, skin, and pituitary and adrenal glands (20,29). From these studies, ascorbic acid is taken up by several tissues by an energy-dependent and Na -sensitive process, but the transport of the oxidized vitamin form follows the principles of diflFusion. 

There must also be a second mechanism of ascorbic acid transport through certain specialized cells, difierent from the diffusion of dehydro-ascorbic acid followed by intracellular reduction. There are no indications that dehydroascorbic acid is involved in the renal tubular absorption of ascorbic acid, and, contrary to earlier conclusions, it appears that the concentration of ascorbic acid into the aqueous humors of the eye occurs in the form of ascorbic acid itself. 

This system cannot now be fitted into known pathways of electron transport, principally because a system that oxidizes ascorbic acid in animal tissues is unknown. The fact is clear, however, that ascorbic acid is oxidized to dehydroascorbic acid in animal tissues and that dehydro-ascorbic add can be reduced. At the very least, this system emphasizes the potential eflBciency of a form of ascorbic acid as an electron acceptor (K3). 

Reduction of dehydroascorbic acid is one of the steps of a potential electron transport system in plants involving ascorbic add oxidase as the terminal oxidation reaction (Eqs. 19). 

Dehydroascorbic acid, the two-electron oxidised form of the vitamin, is taken up on the glucose transporter and reduced to ascorbate to a much greater extent than ascorbate itself is accumulated in human monocytic U-937 cells (May et al. 1999). In contrast to de droascorbic acid, ascorbate enters the cells in a sodium- and energy-dependent transporter. 

Rautenkranz, A. A. F., Li, L., Miichler, F., MMnoia, E., and Oertli, J. J., 1994, Transport of ascorbic and dehydroascorbic acids across protoplast and vacuole membranes isolated from barley Hordeum vulgare L. cv Gerbel) leaves. Plant Physiol. 106 187-193. 

Vera, J. C., Rivas, C. I., Fischbarg, J., and Golde, D. W., 1993, Mammalian facilitative hexose transporters mediate the transport of dehydroascorbic acid. Nature 364 79-82. 

The ingested amounts of vitamin C are mainly absorbed in the duodenum, in the proximal jejunum, and through the buccal mucous membrane. The physiological daily intake of vitamin C of up to 180 mg is absorbed 80 to 90%. In humans and guinea pigs the absorption mechanism of L-ascorbate depends on a pH-dependent saturable active transport and relies on the presence of a carrier and sodium ions. Dehydroascorbic acid is absorbed by facilitated diffusion. For animals with the... 

Ascorbic acid in blood is transported by a reversible complex with serum albumin (Moloy et al., 1980). The main transport form of vitamin C seems to be the reduced molecule. The concentration of dehydroascorbic acid can, however, exceed that of ascorbic acid in vitamin C deficiency and certain diseases (Stone, 1977). The relation of ascorbic acid/dehydroascorbic acid in human plasma decreases also with age (Sasaki et al., 1983). Since the typical screening methods for the determination of vitamin C status in blood are not able to distinguish between the different circulating forms of vitamin C, it has to be clearly stated that the detailed interpretation of vitamin C status and its relation to certain disorders must reflect on both ascorbic acid and dehydroascorbic acid concentration in blood. 

Vitamin C is transported into the blood cells in its oxidized form as dehydroascorbic acid, since this form is non-ionized under physiological conditions and is therefore permeable for membranes. It has been postulated that at least human neutrophils are able to oxidize extracellular ascorbic acid for a more efficient uptake into the cells (Washko et al., 1993). This mechanism also represents a part of the biological recycling system for antioxidants. The intracellular dehydroascorbic acid is rapidly reduced again to ascorbic acid by the GSH redox system. This reduction might also be mediated by the still hypothetical dehydroascorbic acid reductase. 

The transport of dehydroascorbic acid into blood cells uses the same system as the transport of glucose. Therefore, the cellular uptake of dehydroascorbic acid depends on the presence of insulin and can be inhibited by high concentrations of glucose. These findings are important for the vitamin C metabolism of diabetics, since several diabetic risk factors (like angiopathies) might be related to a lack of ascorbic acid (Verlangieri et al., 1981). 

Contrary to the active carrier-mediated transport of ascorbic acid into the cell, the intracellular transport into organelles like mitochondria follows carrier-free diffusion of both ascorbic acid and dehydroascorbic acid. Intramitochondrial dehydroascorbic acid is not reduced to ascorbic acid (Ingebretsen et al., 1982). 

Rumsey, S. C. Kwon, O. Xu, G. W. Burant, C. F. Simpson, L Levine, M. 1997. Glucose transporter isoforms GLUTl and GLUT3 transport dehydroascorbic acid. J. Biol. Chem. 272 18982-18989. 

It has been known for some time that there exists a close correlation between the ascorbic acid and glutathione content of plant tissues. Plant tissues are also known to contain dehydroascorbic reductase, which catalyzes the transfer of hydrogens from GSH to dehydroascorbic acid, as well as ascorbic acid oxidase. Mapson and Goddard have, therefore, provided a possible scheme for hydrogen transport which does not involve the cytochrome system. The hydrogens may take the following pathway ... 

Ascorbate oxidase is a tetramer each subunit has 552 amino acids and contains 4 copper ions, the type-I blue copper center and the adjacent trinuclear center (arranged as a type-n center and a type-in dinuclear center) separated by /S-sheets (Figure 20) °. Ascorbate is oxidized to dehydroascorbate by dioxygen however, it is not bound directly to the metal center to be oxidized, but is proposed to bind near the type-I Cu site which may facihtate electron transfer to oxygen, presumably in the tri-Cu cluster site. Since humans cannot synthesize ascorbic acid, conservation of this important compound is highly regulated. For example, the oxidized ascorbate can be transported into red blood... 

---