Quick Matthias, Shi Lei
Department of Psychiatry, Division of Molecular Therapeutics, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York, USA.
Department of Physiology and Biophysics, Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, USA.
Vitam Horm. 2015;98:63-100. doi: 10.1016/bs.vh.2014.12.003. Epub 2015 Mar 7.
The Na(+)/multivitamin transporter (SMVT) is a member of the solute:sodium symporter family that catalyzes the Na(+)-dependent uptake of the structurally diverse water-soluble vitamins pantothenic acid (vitamin B5) and biotin (vitamin H), α-lipoic acid-a vitamin-like substance with strong antioxidant properties-and iodide. The organic substrates of SMVT play central roles in the cellular metabolism and are, therefore, essential for normal human health and development. For example, biotin deficiency leads to growth retardation, dermatological disorders, and neurological disorders. Animal studies have shown that biotin deficiency during pregnancy is directly correlated to embryonic growth retardation, congenital malformation, and death of the embryo. This chapter focuses on the structural and functional features of the human isoform of SMVT (hSMVT); the discovery of which was greatly facilitated by the cloning and expression of hSMVT in tractable expression systems. Special emphasis will be given to mechanistic implications of the transport process of hSMVT that will inform our understanding of the molecular determinants of hSMVT-mediated transport in dynamic context to alleviate the development and optimization of hSMVT as a multipotent platform for drug delivery.
钠/多种维生素转运体（SMVT）是溶质：钠同向转运体家族的成员，它催化结构多样的水溶性维生素泛酸（维生素B5）、生物素（维生素H）、具有强抗氧化特性的类维生素物质α-硫辛酸以及碘化物的钠依赖性摄取。SMVT的有机底物在细胞代谢中起核心作用，因此对人类正常健康和发育至关重要。例如，生物素缺乏会导致生长发育迟缓、皮肤病和神经疾病。动物研究表明，孕期生物素缺乏与胚胎生长发育迟缓、先天性畸形及胚胎死亡直接相关。本章重点关注人源SMVT异构体（hSMVT）的结构和功能特征；hSMVT在易处理表达系统中的克隆和表达极大地推动了其发现。将特别强调hSMVT转运过程的机制意义，这将有助于我们在动态背景下理解hSMVT介导转运的分子决定因素，以促进hSMVT作为多能药物递送平台的开发和优化。
