A family of mammalian Na+-dependent L-ascorbic acid transporters

Abstract

Vitamin C (L-ascorbic acid) is essential for many enzymatic reactions, in which it serves to maintain prosthetic metal ions in their reduced forms (for example, Fe2+, Cu+)1,2, and for scavenging free radicals in order to protect tissues from oxidative damage3. The facilitative sugar transporters of the GLUT type can transport the oxidized form of the vitamin, dehydroascorbic acid4,5,6, but these transporters are unlikely to allow significant physiological amounts of vitamin C to be taken up in the presence of normal glucose concentrations, because the vitamin is present in plasma essentially only in its reduced form7. Here we describe the isolation of two L-ascorbic acid transporters, SVCT1 and SVCT2, from rat complementary DNA libraries, as the first step in investigating the importance of L-ascorbic acid transport in regulating the supply and metabolism of vitamin C. We find that SVCT1 and SVCT2 each mediate concentrative, high-affinity L-ascorbic acid transport that is stereospecific and is driven by the Na+ electrochemical gradient. Despite their close sequence homology and similar functions, the two isoforms of the transporter are discretely distributed: SVCT1 is mainly confined to epithelial systems (intestine, kidney, liver), whereas SVCT2 serves a host of metabolically active cells and specialized tissues in the brain, eye and other organs.

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Figure 1: Sequence and putative membrane topology of SVCT1 and SVCT2.
Figure 2: Functional characterization of SVCT expressed in Xenopus oocytes.
Figure 3: Localization of SVCT1 and SVCT2 mRNA in rat tissues detected by insitu hybridization.
Figure 4: Localization of SVCT2 mRNA in the albino rabbit eye detected by in situ hybridization.

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Acknowledgements

We thank E. Brown for providing MC3T3-E1 cells and P. Fong for providing the pTLN2 vector. This research was supported by the NIH, the National Kidney Foundation, the American Heart Association Massachusetts Affiliate, Cooley's Anemia Foundation, and the International Human Frontier Science Program.

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Correspondence to Matthias A. Hediger.

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Tsukaguchi, H., Tokui, T., Mackenzie, B. et al. A family of mammalian Na+-dependent L-ascorbic acid transporters. Nature 399, 70–75 (1999). https://doi.org/10.1038/19986

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