Transport model of the human Na+-coupled L-ascorbic acid (vitamin C) transporter SVCT1

被引:25
|
作者
Mackenzie, Bryan [1 ,3 ,4 ,5 ]
Illing, Anthony C. [1 ]
Hediger, Matthias A. [2 ,3 ,4 ,5 ]
机构
[1] Univ Cincinnati, Coll Med, Dept Mol & Cellular Physiol, Cincinnati, OH 45267 USA
[2] Univ Bern, Inst Biochem & Mol Med, Bern, Switzerland
[3] Harvard Univ, Sch Med, Boston, MA 02115 USA
[4] Brigham & Womens Hosp, Dept Med, Membrane Biol Program, Boston, MA 02115 USA
[5] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA
来源
关键词
cotransporters; sodium dependent; intestinal absorption; model simulation; renal reabsorption; Xenopus oocyte;
D O I
10.1152/ajpcell.00439.2007
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Vitamin C (L-ascorbic acid) is an essential micronutrient that serves as an antioxidant and as a cofactor in many enzymatic reactions. Intestinal absorption and renal reabsorption of the vitamin is mediated by the epithelial apical L-ascorbic acid cotransporter SVCT1 (SLC23A1). We explored the molecular mechanisms of SVCT1-mediated L-ascorbic acid transport using radio-tracer and voltage-clamp techniques in RNA-injected Xenopus oocytes. L-Ascorbic acid transport was saturable (K-0.5 approximate to 70 mu M), temperature dependent (Q(10) approximate to 5), and energized by the Na+ electrochemical potential gradient. We obtained a Na+ -L-ascorbic acid coupling ratio of 2:1 from simultaneous measurement of currents and fluxes. L-Ascorbic acid and Na+ saturation kinetics as a function of cosubstrate concentrations revealed a simultaneous transport mechanism in which binding is ordered Na+, L-ascorbic acid, Na+. In the absence of L-ascorbic acid, SVCT1 mediated pre-steady-state currents that decayed with time constants 3-15 ms. Transients were described by single Boltzmann distributions. At 100 mM Na+, maximal charge translocation (Q(max)) was approximate to 25 nC, around a midpoint (V-0.5) at -9 mV, and with apparent valence approximate to-1. Q(max) was conserved upon progressive removal of Na+, whereas V-0.5 shifted to more hyperpolarized potentials. Model simulation predicted that the pre-steady-state current predominantly results from an ion-well effect on binding of the first Na+ partway within the membrane electric field. We present a transport model for SVCT1 that will provide a framework for investigating the impact of specific mutations and polymorphisms in SLC23A1 and help us better understand the contribution of SVCT1 to vitamin C metabolism in health and disease.
引用
收藏
页码:C451 / C459
页数:9
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