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

Vitamin C (L-ascorbic acid) is essential for many enzymatic reactions, in w hich it serves to maintain prosthetic metal ions in their reduced forms (fo r example, Fe2+, Cu+)(1,2), and for scavenging free radicals in order to pr otect tissues from oxidative damage(3). The facilitative sugar transporters of the GLUT type can transport the oxidized form of the vitamin, dehydroas corbic acid(4-6), 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 essential ly only in its reduced form(7). Here we describe the isolation of two L-asc orbic acid transporters, SVCT1 and SVCT2, from rat complementary DNA librar ies, as the first step in investigating the importance of L-ascorbic acid t ransport 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 g radient. Despite their close sequence homology and similar functions, the t wo isoforms of the transporter are discretely distributed: SVCT1 is mainly confined to epithelial systems (intestine, kidney, liver), whereas SVCT2 se rves a host of metabolically active cells and specialized tissues in the br ain, ey and other organs.