Human vitamin C (L-ascorbic acid) transporter SVCT1.
In human, vitamin C (l-ascorbic acid) is an essential micronutrient required for an array of biological functions including enzymatic reactions and antioxidation. We describe here the molecular cloning of a novel human cDNA encoding a vitamin C transporter SVCT1. SVCT1 is largely confined to bulk-transporting epithelia (e.g., kidney and small intestine) with a putative alternative-splice product present in thymus. Applying radiotracer and voltage-clamp approaches in cRNA-injected Xenopus oocytes, we found that SVCT1 mediates saturable, concentrative, high-affinity l-ascorbic acid transport (K(0.5) = 50-100 microM) that is electrogenic and can be inhibited by phloretin. SVCT1 displays exquisite substrate selectivity, greatly favoring l-ascorbic acid over its isomers d-isoascorbic acid and dehydroascorbic acid and 2- or 6-substituted analogues, whereas glucose and nucleobases are excluded. We have mapped the SLC23A2 gene (coding for SVCT1) to human chromosome 5 in band 5q31.2-31.3, within a region commonly deleted in malignant myeloid (leukemia) diseases. In addition, we have demonstrated that the human SLC23A1 gene product is a related high-affinity l-ascorbic acid transporter (SVCT2) that is widely distributed in brain, retina, and a host of endocrine and neuroendocrine tissues. The molecular identification of the human l-ascorbic acid transporters now provides the tools with which to investigate their roles in vitamin C metabolism in health and disease.
Wang
Y
Y
Membrane Biology Program and Renal Division, Department of Pathology, Department of Obstetrics, Gynecology & Reproductive Biology, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Mackenzie
B
B
Tsukaguchi
H
H
Weremowicz
S
S
Morton
C C
CC
Hediger
M A
MA
D000595:Amino Acid Sequence; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D001483:Base Sequence; D001693:Biological Transport, Active; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D066298:In Vitro Techniques; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D014982:Xenopus laevis
D017931:DNA Primers; D018076:DNA, Complementary; D029363:Organic Anion Transporters, Sodium-Dependent; D011506:Proteins; D011994:Recombinant Proteins; C555162:SLC23A1 protein, human; C555163:SLC23A2 protein, human; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D001205:Ascorbic Acid