The B vitamins folic acid and thiamine are transported across the cell membrane, particularly in the intestine, kidneys and placenta, using pH differences as driving forces. Topological modelling suggests the transporters have 12 TM domains.

Loss-of-function mutations in ThTr1 underlie thiamine-responsive megaloblastic anemia syndrome [2].

* Key recommended reading is highlighted with an asterisk

Ganapathy V, Smith SB, Prasad PD. (2004) SLC19: the folate/thiamine transporter family. Pflugers Arch, 447 (5): 641-6. [PMID:14770311]

Goldman ID, Chattopadhyay S, Zhao R, Moran R. (2010) The antifolates: evolution, new agents in the clinic, and how targeting delivery via specific membrane transporters is driving the development of a next generation of folate analogs. Curr Opin Investig Drugs, 11 (12): 1409-23. [PMID:21154123]

Hou Z, Matherly LH. (2014) Biology of the major facilitative folate transporters SLC19A1 and SLC46A1. Curr Top Membr, 73: 175-204. [PMID:24745983]

Matherly LH, Hou Z. (2008) Structure and function of the reduced folate carrier a paradigm of a major facilitator superfamily mammalian nutrient transporter. Vitam Horm, 79: 145-84. [PMID:18804694]

* Matherly LH, Wilson MR, Hou Z. (2014) The major facilitative folate transporters solute carrier 19A1 and solute carrier 46A1: biology and role in antifolate chemotherapy of cancer. Drug Metab Dispos, 42 (4): 632-49. [PMID:24396145]

Yuasa H, Inoue K, Hayashi Y. (2009) Molecular and functional characteristics of proton-coupled folate transporter. J Pharm Sci, 98 (5): 1608-16. [PMID:18823045]

Zhao R, Diop-Bove N, Visentin M, Goldman ID. (2011) Mechanisms of membrane transport of folates into cells and across epithelia. Annu Rev Nutr, 31: 177-201. [PMID:21568705]

* Zhao R, Goldman ID. (2013) Folate and thiamine transporters mediated by facilitative carriers (SLC19A1-3 and SLC46A1) and folate receptors. Mol Aspects Med, 34 (2-3): 373-85. [PMID:23506878]

1. Assaraf YG, Babani S, Goldman ID. (1998) Increased activity of a novel low pH folate transporter associated with lipophilic antifolate resistance in chinese hamster ovary cells. J Biol Chem, 273 (14): 8106-11. [PMID:9525913]

2. Diaz GA, Banikazemi M, Oishi K, Desnick RJ, Gelb BD. (1999) Mutations in a new gene encoding a thiamine transporter cause thiamine-responsive megaloblastic anaemia syndrome. Nat Genet, 22 (3): 309-12. [PMID:10391223]

3. Dutta B, Huang W, Molero M, Kekuda R, Leibach FH, Devoe LD, Ganapathy V, Prasad PD. (1999) Cloning of the human thiamine transporter, a member of the folate transporter family. J Biol Chem, 274 (45): 31925-9. [PMID:10542220]

4. Prasad PD, Ramamoorthy S, Leibach FH, Ganapathy V. (1995) Molecular cloning of the human placental folate transporter. Biochem Biophys Res Commun, 206 (2): 681-7. [PMID:7826387]

5. Rajgopal A, Edmondnson A, Goldman ID, Zhao R. (2001) SLC19A3 encodes a second thiamine transporter ThTr2. Biochim Biophys Acta, 1537 (3): 175-8. [PMID:11731220]

6. Rosowsky A, Forsch RA, Wright JE. (2004) Synthesis and in vitro antifolate activity of rotationally restricted aminopterin and methotrexate analogues. J Med Chem, 47 (27): 6958-63. [PMID:15615544]

7. Zhao R, Gao F, Goldman ID. (2002) Reduced folate carrier transports thiamine monophosphate: an alternative route for thiamine delivery into mammalian cells. Am J Physiol, Cell Physiol, 282 (6): C1512-7. [PMID:11997266]