title: The sodium/multivitamin transporter: a multipotent system with therapeutic implications.
abstract: 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.
authors.affiliation: Department of Psychiatry, Division of Molecular Therapeutics, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York, USA. Electronic address: mq2102@columbia.edu.
authors.forename: Matthias
authors.initials: M
authors.lastname: Quick
authors.affiliation: Department of Physiology and Biophysics, Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
mesh_terms: D001692:Biological Transport / Q000502:physiology; D006801:Humans; D026901:Membrane Transport Proteins / Q000502:physiology*; D020033:Protein Isoforms / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D027981:Symporters / Q000502:physiology; D014815:Vitamins / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; D020033:Protein Isoforms; D027981:Symporters; D014815:Vitamins; D012964:Sodium
keywords: Biotin; Lipoic acid; Na(+)-coupled transport; Pantothenic acid; SLC5; Sodium/multivitamin transporter; Solute:sodium symporter family
references.citation: J Mol Cell Cardiol. 1990 Mar;22(3):323-32
references.pmid: 2141362
references.citation: Nature. 2014 Jan 23;505(7484):569-73
references.pmid: 24317697
references.citation: J Biol Chem. 2001 Jan 19;276(3):1728-34
references.pmid: 11024018
references.citation: Eur J Clin Chem Clin Biochem. 1992 Mar;30(3):119-26
references.pmid: 1599976
references.citation: Int J Vitam Nutr Res. 1999 Mar;69(2):113-9
references.pmid: 10218148
references.citation: Mol Biol Evol. 2000 Apr;17(4):540-52
references.pmid: 10742046
references.citation: Am J Clin Dermatol. 2002;3(6):427-33
references.pmid: 12113650
references.citation: Mol Cell. 2008 Jun 20;30(6):667-77
references.pmid: 18570870
references.citation: Am J Physiol Cell Physiol. 2010 Jan;298(1):C124-31
references.pmid: 19864324
references.citation: Biofactors. 1998;8(1-2):17-21
references.pmid: 9699003
references.citation: Structure. 2014 May 6;22(5):769-80
references.pmid: 24768113
references.citation: Science. 2010 Apr 23;328(5977):470-3
references.pmid: 20413494
references.citation: Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):E1571-80
references.pmid: 24711390
references.citation: Nature. 1966 Aug 27;211(5052):969-70
references.pmid: 5968307
references.citation: BMC Bioinformatics. 2006 Oct 10;7:439
references.pmid: 17032440
references.citation: Science. 2003 Aug 1;301(5633):610-5
references.pmid: 12893935
references.citation: Am J Physiol Cell Physiol. 2009 Apr;296(4):C654-62
references.pmid: 19052257
references.citation: Proc Soc Exp Biol Med. 2000 Jan;223(1):14-21
references.pmid: 10632957
references.citation: J Nutr. 1999 Feb;129(2S Suppl):490S-493S
references.pmid: 10064315
references.citation: Am J Clin Nutr. 2002 Feb;75(2):295-9
references.pmid: 11815321
references.citation: Curr Opin Neurobiol. 2005 Jun;15(3):296-304
references.pmid: 15919190
references.citation: J Invest Dermatol. 2003 Mar;120(3):428-33
references.pmid: 12603856
references.citation: Pflugers Arch. 1994 Jan;426(1-2):121-8
references.pmid: 8146015
references.citation: J Biol Chem. 1998 Mar 27;273(13):7501-6
references.pmid: 9516450
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16504-9
references.pmid: 17925435
references.citation: J Physiol. 1959 Sep 2;147:260-8
references.pmid: 13791672
references.citation: Nature. 2007 Oct 11;449(7163):726-30
references.pmid: 17704762
references.citation: Am J Physiol. 1990 Nov;259(5 Pt 1):G865-72
references.pmid: 2240226
references.citation: J Nutr Biochem. 1999 Mar;10(3):128-38
references.pmid: 15539280
references.citation: J Biol Chem. 1997 Jan 24;272(4):2110-5
references.pmid: 8999910
references.citation: N Engl J Med. 1983 Mar 17;308(11):639-42
references.pmid: 6828095
references.citation: Biochemistry. 2013 Sep 17;52(37):6568-74
references.pmid: 23962108
references.citation: Nature. 2011 Jun 2;474(7349):109-13
references.pmid: 21516104
references.citation: Int J Pharm. 2012 Sep 15;434(1-2):315-24
references.pmid: 22692074
references.citation: Methods Enzymol. 1998;293:123-45
references.pmid: 9711606
references.citation: Nature. 2010 Sep 9;467(7312):233-6
references.pmid: 20829798
references.citation: Curr Opin Gastroenterol. 2006 Mar;22(2):140-6
references.pmid: 16462170
references.citation: J Membr Biol. 1997 Sep 1;159(1):1-20
references.pmid: 9309206
references.citation: J Mol Microbiol Biotechnol. 2012;22(2):105-13
references.pmid: 22627175
references.citation: Brain Res. 2000 Mar 10;858(2):348-55
references.pmid: 10708686
references.citation: Lancet. 1981 Aug 1;2(8240):263
references.pmid: 6114319
references.citation: Nature. 2009 May 21;459(7245):347-55
references.pmid: 19458710
references.citation: J Biol Chem. 2001 Oct 19;276(42):38329-36
references.pmid: 11477096
references.citation: Free Radic Biol Med. 1997;22(1-2):359-78
references.pmid: 8958163
references.citation: Annu Rev Physiol. 2004;66:419-46
references.pmid: 14977409
references.citation: J Nutr. 1983 Mar;113(3):574-81
references.pmid: 6827377
references.citation: Curr Opin Cell Biol. 1996 Aug;8(4):468-73
references.pmid: 8791459
references.citation: Altern Med Rev. 2011 Sep;16(3):263-74
references.pmid: 21951027
references.citation: J Membr Biol. 1992 Jan;125(1):63-79
references.pmid: 1294062
references.citation: J Biol Chem. 1998 Oct 9;273(41):26400-7
references.pmid: 9756872
references.citation: J Mol Biol. 1982 May 5;157(1):105-32
references.pmid: 7108955
references.citation: Fed Proc. 1965 Sep-Oct;24(5):1000-6
references.pmid: 5838166
references.citation: J Membr Biol. 1998 Mar 15;162(2):101-6
references.pmid: 9538503
references.citation: Q Rev Biophys. 1997 Nov;30(4):333-64
references.pmid: 9634651
references.citation: J Membr Biol. 1997 Jan 15;155(2):175-86
references.pmid: 9049111
references.citation: J Child Neurol. 2002 Feb;17(2):146
references.pmid: 11952077
references.citation: J Am Acad Dermatol. 1989 Jul;21(1):1-30
references.pmid: 2663932
references.citation: J Nutr. 2005 Jun;135(6 Suppl):1527S-30S
references.pmid: 15930464
references.citation: Am J Physiol. 1999 Oct;277(4 Pt 1):C605-13
references.pmid: 10516089
references.citation: Int J Vitam Nutr Res. 2002 Jul;72(4):195-8
references.pmid: 12214555
references.citation: J Biol Chem. 1996 Jan 26;271(4):1925-34
references.pmid: 8567640
references.citation: Trends Neurosci. 2004 Jun;27(6):352-9
references.pmid: 15165740
references.citation: J Gen Physiol. 2005 Jan;125(1):13-36
references.pmid: 15596535
references.citation: Clin Chim Acta. 1990 Aug 31;189(3):313-25
references.pmid: 2225462
references.citation: J Biol Chem. 1998 Aug 28;273(35):22657-63
references.pmid: 9712895
references.citation: Pflugers Arch. 2004 Feb;447(5):465-8
references.pmid: 14624363
references.citation: Am J Physiol Gastrointest Liver Physiol. 2011 Apr;300(4):G561-7
references.pmid: 21183659
references.citation: Nature. 2000 Nov 9;408(6809):239-47
references.pmid: 11089981
references.citation: Physiol Rev. 2011 Apr;91(2):733-94
references.pmid: 21527736
references.citation: Science. 1990 Sep 14;249(4974):1303-6
references.pmid: 1975955
references.citation: J Mol Microbiol Biotechnol. 2006;11(6):289-90
references.pmid: 17114892
references.citation: Biochemistry. 1988 Jan 12;27(1):12-7
references.pmid: 3349023
references.citation: Nat Struct Mol Biol. 2010 Apr;17(4):492-6
references.pmid: 20357772
references.citation: Curr Top Med Chem. 2013;13(7):837-42
references.pmid: 23578027
references.citation: J Biol Chem. 1994 Aug 26;269(34):21407-10
references.pmid: 8063771
references.citation: Nature. 2010 Dec 16;468(7326):988-91
references.pmid: 21131949
references.citation: Science. 2008 Aug 8;321(5890):810-4
references.pmid: 18599740
references.citation: Science. 1991 Oct 25;254(5031):578-9
references.pmid: 1948035
references.citation: Mol Gen Genet. 1987 Jun;208(1-2):70-5
references.pmid: 3302614
references.citation: Microbiol Mol Biol Rev. 2000 Jun;64(2):354-411
references.pmid: 10839820
references.citation: Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W465-9
references.pmid: 18424797
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3856-8
references.pmid: 12824436
references.citation: Vitam Horm. 1991;46:165-228
references.pmid: 1746161
references.citation: J Biol Chem. 1966 Nov 25;241(22):5201-4
references.pmid: 5333155
references.citation: Free Radic Biol Med. 1998 Apr;24(6):1023-39
references.pmid: 9607614
references.citation: Methods Enzymol. 1979;62:152-8
references.pmid: 374970
references.citation: Proc Nutr Soc. 1999 May;58(2):427-33
references.pmid: 10466187
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):1760-5
references.pmid: 19181854
references.citation: Nutrition. 1997 Nov-Dec;13(11-12):941-4
references.pmid: 9433708
references.citation: Am J Physiol Cell Physiol. 2009 Apr;296(4):C663-71
references.pmid: 19211916
references.citation: Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G275-81
references.pmid: 16959947
references.citation: Nucleic Acids Res. 2004 Mar 19;32(5):1792-7
references.pmid: 15034147
references.citation: Pflugers Arch. 2004 Feb;447(5):510-8
references.pmid: 12748858
references.citation: J Biol Chem. 2000 Dec 1;275(48):37414-22
references.pmid: 10973981
references.citation: Free Radic Biol Med. 1995 Aug;19(2):227-50
references.pmid: 7649494
references.citation: J Biol Chem. 2005 Jan 21;280(3):2244-56
references.pmid: 15528186
references.citation: Fed Proc. 1962 Nov-Dec;21:891-5
references.pmid: 14023681
references.citation: Am J Physiol Cell Physiol. 2007 Apr;292(4):C1305-12
references.pmid: 17135299
references.citation: Endocrinology. 1957 Jul;61(1):93-7
references.pmid: 13437959
references.citation: Curr Drug Targets. 2012 Jun;13(7):994-1003
references.pmid: 22420308
references.citation: Proc Natl Acad Sci U S A. 1993 Jun 15;90(12 ):5767-71
references.pmid: 8516326
references.citation: Nat Rev Mol Cell Biol. 2001 Aug;2(8):610-20
references.pmid: 11483994
references.citation: Annu Rev Nutr. 1986;6:317-43
references.pmid: 3089241
references.citation: Helv Paediatr Acta. 1982;37(5):499-502
references.pmid: 6819258
references.citation: J Biol Chem. 1995 Nov 10;270(45):27099-105
references.pmid: 7592962
references.citation: Placenta. 1997 Sep;18(7):527-33
references.pmid: 9290147
references.citation: Curr Med Chem. 2004 May;11(9):1135-46
references.pmid: 15134511
references.citation: Biochim Biophys Acta. 2011 Aug;1808(8):2073-80
references.pmid: 21570947
references.citation: Drug Nutr Interact. 1988;5(4):317-43
references.pmid: 3240713
references.citation: J Synchrotron Radiat. 2011 Jan;18(1):20-3
references.pmid: 21169684
references.citation: Proc Natl Acad Sci U S A. 2014 Feb 4;111(5):1784-8
references.pmid: 24453216
references.citation: Nature. 1985 Jul 18-24;316(6025):234-8
references.pmid: 2410791
references.citation: Nature. 1987 Nov 26-Dec 2;330(6146):379-81
references.pmid: 2446136
references.citation: Subcell Biochem. 2012;56:1-19
references.pmid: 22116691
references.citation: Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9209-13
references.pmid: 8105473
references.citation: J Inherit Metab Dis. 1984;7 Suppl 2:121-2
references.pmid: 6434861
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15294-8
references.pmid: 17881559
references.citation: Syst Biol. 2003 Oct;52(5):696-704
references.pmid: 14530136
references.citation: Dermatol Ther (Heidelb). 2014 Jun;4(1):93-101
references.pmid: 24831048
references.citation: Toxicol Appl Pharmacol. 2002 Jul 1;182(1):84-90
references.pmid: 12127266
references.citation: Am J Physiol Cell Physiol. 2011 Jan;300(1):C97-104
references.pmid: 20962270
references.citation: Chem Biol. 2003 Dec;10 (12 ):1293-302
references.pmid: 14700636
references.citation: J Membr Biol. 1989 Aug;110(1):87-95
references.pmid: 2795642
references.citation: J Pediatr. 1957 Nov;51(5):537-48
references.pmid: 13476338
references.citation: J Lab Clin Med. 1992 Jun;119(6):598-620
references.pmid: 1593209
references.citation: J Biol Chem. 1992 Nov 15;267(32):22902-6
references.pmid: 1429639
references.citation: Am J Physiol. 1998 Aug;275(2 Pt 1):C382-8
references.pmid: 9688592
references.citation: Am J Physiol. 1989 Feb;256(2 Pt 1):G306-11
references.pmid: 2919673
references.citation: J Chromatogr B Biomed Appl. 1996 Apr 26;679(1-2):41-7
references.pmid: 8998568
references.citation: Nature. 2005 Sep 8;437(7056):215-23
references.pmid: 16041361
references.citation: Science. 2008 Oct 31;322(5902):709-13
references.pmid: 18927357
references.citation: J Biol Chem. 2011 Mar 11;286(10):7975-82
references.pmid: 21187287
references.citation: Proc Natl Acad Sci U S A. 1989 Aug;86(15):5748-52
references.pmid: 2490366
references.citation: J Exp Biol. 1994 Nov;196:197-212
references.pmid: 7823022
references.citation: Physiology (Bethesda). 2004 Dec;19:370-6
references.pmid: 15546855
references.citation: J Biol Chem. 2011 Aug 19;286(33):29347-55
references.pmid: 21705334
references.citation: Am J Physiol Gastrointest Liver Physiol. 2003 Jul;285(1):G73-7
references.pmid: 12646417
references.citation: J Cell Biochem. 1999;Suppl 32-33:84-94
references.pmid: 10629107
references.citation: Gastroenterology. 1988 May;94(5 Pt 1):1157-63
references.pmid: 3350285
references.citation: Am J Clin Nutr. 1971 May;24(5):513-23
references.pmid: 5578511
references.citation: Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8597-601
references.pmid: 12077304
references.citation: Prog Lipid Res. 2005 Mar-May;44(2-3):125-53
references.pmid: 15893380
references.citation: Adv Nutr. 2012 Mar 01;3(2):213-4
references.pmid: 22516729
references.citation: Annu Rev Nutr. 2005;25:175-96
references.pmid: 16011464
references.citation: Arch Biochem Biophys. 1999 Jun 1;366(1):95-106
references.pmid: 10334869
references.citation: FASEB J. 1991 Jul;5(10):2482-5
references.pmid: 2065895
references.citation: Am J Physiol. 1964 Mar;206:653-7
references.pmid: 14161000
references.citation: J Neurochem. 1987 Feb;48(2):400-4
references.pmid: 3098919
references.citation: Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9361-6
references.pmid: 21593407
references.citation: Annu Rev Biophys Biomol Struct. 2006;35:67-91
references.pmid: 16689628
references.citation: Toxicol Appl Pharmacol. 1992 May;114(1):88-96
references.pmid: 1585376
references.citation: Int J Pharm. 2013 Jan 30;441(1-2):535-43
references.pmid: 23142496
references.citation: Biofactors. 2009 Jan-Feb;35(1):36-46
references.pmid: 19319844
references.citation: J Nutr. 2009 Jan;139(1):158-62
references.pmid: 19056639
references.citation: J Membr Biol. 1992 Jan;125(1):49-62
references.pmid: 1542106
references.citation: J Bacteriol. 1985 Jun;162(3):1156-61
references.pmid: 3888959
references.citation: Biochemistry. 1999 Oct 12;38(41):13523-9
references.pmid: 10521259
references.citation: Eur J Biochem. 1996 Aug 1;239(3):732-6
references.pmid: 8774720
references.citation: Nat Struct Mol Biol. 2014 May;21(5):472-9
references.pmid: 24747939
references.citation: J Biol Chem. 1995 Jul 28;270(30):17668-71
references.pmid: 7629063
references.citation: Pharmacol Rep. 2011;63(4):849-58
references.pmid: 22001972
references.citation: Pflugers Arch. 1993 Feb;422(5):499-505
references.pmid: 8474852
references.citation: Ann N Y Acad Sci. 1985;447:86-96
references.pmid: 2861781
references.citation: Biochemistry. 1997 Apr 15;36(15):4631-6
references.pmid: 9109673
references.citation: Semin Dermatol. 1991 Dec;10(4):296-302
references.pmid: 1764357
references.citation: Endocr Rev. 2003 Feb;24(1):48-77
references.pmid: 12588808
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20250-5
references.pmid: 18077370
references.citation: J Biol Chem. 2006 Feb 17;281(7):4364-70
references.pmid: 16308322
references.citation: J Biol Chem. 1992 Sep 5;267(25):17760-5
references.pmid: 1381353
references.citation: J Biol Chem. 1997 Oct 24;272(43):27230-8
references.pmid: 9341168
references.citation: FASEB J. 1997 Feb;11(2):118-24
references.pmid: 9039953
references.citation: Gastroenterology. 1988 Jan;94(1):68-72
references.pmid: 3335300
references.citation: Curr Opin Struct Biol. 2009 Aug;19(4):425-32
references.pmid: 19631523
references.citation: Biochemistry. 1998 Sep 29;37(39):13800-6
references.pmid: 9753469
references.citation: Biochemistry. 1998 Aug 4;37(31):11083-8
references.pmid: 9693004
references.citation: Biochim Biophys Acta. 2012 Jan;1818(1):97-102
references.pmid: 22015582
references.citation: Science. 1985 Sep 6;229(4717):941-5
references.pmid: 3839598
references.citation: J Gen Physiol. 1998 Jul;112(1):1-18
references.pmid: 9649580
references.citation: Science. 2009 Aug 21;325(5943):1010-4
references.pmid: 19608859
references.citation: J Membr Biol. 2011 Jan;239(1-2):85-93
references.pmid: 21161516
references.citation: Biochim Biophys Acta. 1994 Jan 3;1189(1):81-8
references.pmid: 7508263
references.citation: Free Radic Biol Med. 2001 Dec 1;31(11):1287-312
references.pmid: 11728801
references.citation: Annu Rev Biochem. 1989;58:195-221
references.pmid: 2673009
references.citation: FEBS Lett. 2002 Oct 2;529(1):73-7
references.pmid: 12354616
references.citation: Nature. 2009 Mar 5;458(7234):47-52
references.pmid: 19262666
references.citation: Nutrition. 2013 May;29(5):796-801
references.pmid: 23510569
references.citation: Biochem J. 1993 Apr 15;291 ( Pt 2):545-51
references.pmid: 8484735
references.citation: Am J Physiol. 1987 Nov;253(5 Pt 1):G631-6
references.pmid: 3120597
references.citation: Annu Rev Nutr. 2002;22:221-39
references.pmid: 12055344
references.citation: Adv Drug Deliv Rev. 2008 Oct-Nov;60(13-14):1463-70
references.pmid: 18655815
references.citation: J Biol Chem. 2011 Jan 7;286(1):131-7
references.pmid: 20980265
references.citation: Pharm Res. 2013 Aug;30(8):2063-76
references.pmid: 23657675
references.citation: Nature. 1996 Feb 1;379(6564):458-60
references.pmid: 8559252
references.citation: Experientia. 1996 Feb 15;52(2):149-54
references.pmid: 8608817
references.citation: Gastroenterology. 1988 Nov;95(5):1312-7
references.pmid: 3169497
references.citation: J Biol Chem. 1999 May 21;274(21):14875-83
references.pmid: 10329687
references.citation: Am J Physiol. 1998 Nov;275(5 Pt 1):C1365-71
references.pmid: 9814986