Tsukaguchi H, Tokui T, Mackenzie B, Berger U V, Chen X Z, Wang Y, Brubaker R F, Hediger M A
Membrane Biology Program, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature. 1999 May 6;399(6731):70-5. doi: 10.1038/19986.
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.
维生素C(L-抗坏血酸)对许多酶促反应至关重要,在这些反应中,它能使辅因子金属离子保持还原态(例如Fe2+、Cu+),并能清除自由基,从而保护组织免受氧化损伤。GLUT型易化性糖转运蛋白能够转运维生素的氧化形式——脱氢抗坏血酸,但在正常葡萄糖浓度存在的情况下,这些转运蛋白不太可能使大量具有生理活性的维生素C被摄取,因为维生素在血浆中基本上仅以还原形式存在。在此,我们描述了从大鼠互补DNA文库中分离出两种L-抗坏血酸转运蛋白SVCT1和SVCT2的过程,这是研究L-抗坏血酸转运在调节维生素C供应和代谢中的重要性的第一步。我们发现,SVCT1和SVCT2均介导具有立体特异性的、由Na+电化学梯度驱动的、高亲和力的L-抗坏血酸浓缩转运。尽管这两种转运蛋白亚型具有密切的序列同源性和相似的功能,但它们的分布却有所不同:SVCT1主要局限于上皮系统(肠道、肾脏、肝脏),而SVCT2则存在于脑、眼及其他器官中的许多代谢活跃细胞和特殊组织中。