title: 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+), and for scavenging free radicals in order to protect tissues from oxidative damage. The facilitative sugar transporters of the GLUT type can transport the oxidized form of the vitamin, dehydroascorbic acid, 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 form. 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.
authors.affiliation: Membrane Biology Program, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: H
authors.initials: H
authors.lastname: Tsukaguchi
authors.forename: T
authors.initials: T
authors.lastname: Tokui
authors.forename: B
authors.initials: B
authors.lastname: Mackenzie
authors.forename: U V
authors.initials: UV
authors.lastname: Berger
authors.forename: X Z
authors.initials: XZ
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: R F
authors.initials: RF
authors.lastname: Brubaker
authors.forename: M A
authors.initials: MA
authors.lastname: Hediger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D001692:Biological Transport; D003001:Cloning, Molecular; D018076:DNA, Complementary; D008969:Molecular Sequence Data; D029363:Organic Anion Transporters, Sodium-Dependent; D011506:Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000378:metabolism*; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D014018:Tissue Distribution; D014981:Xenopus
chemical_list: D018076:DNA, Complementary; D029363:Organic Anion Transporters, Sodium-Dependent; D011506:Proteins; C555166:Slc23a1 protein, rat; C555167:Slc23a2 protein, rat; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D012964:Sodium; D001205:Ascorbic Acid