SLC19: the folate/thiamine transporter family

Abstract

The SLC19 gene family of solute carriers is a family of three transporter proteins with significant structural similarity, transporting, however, substrates with different structure and ionic charge. The three members of this gene family are expressed ubiquitously and mediate the transport of two important water-soluble vitamins, folate and thiamine. The concentrative transport of substrates mediated by the members of this gene family is energized by transcellular H(+)/OH(-) gradient. SLC19A1 is expressed at highest levels in absorptive cells where it is located in a polarized manner either in the apical or basal membrane, depending on the cell type. It mediates the transport of reduced folate and its analogs, such as methotrexate, which are anionic at physiological pH. SLC19A2 is expressed ubiquitously and mediates the transport of thiamine, a cation at physiological pH. SLC19A3 is also widely expressed and is capable of transporting thiamine. This review summarizes the current knowledge on the structural, functional, molecular and physiological aspects of the SLC19 gene family.

Linear Chain PEGylated Recombinant Bacillus Thiaminolyticus Thiaminase I Enzyme Has Growth Inhibitory Activity against Lymphoid Leukemia Cell Lines

“…Thiamine is transported into the cell by either of 2 thiamine transport proteins, where it is quickly phosphorylated into its active cofactor forms (9). Thiamine phosphates play a central role in enzymes regulating how both energy and glucose carbon are used by the cell (10).…”

Hypoxia induced upregulation and function of the thiamine transporter, SLC19A3 in a breast cancer cell line

“…SLC19A3 belongs to the SLC19 gene family comprising the folate transporter SLC19A1 (RFC1) and two thiamine transporters SLC19A2 (THTR1) and SLC19A3 (THTR2). 38 Both THTR1 and THTR2 contribute to the intracellular uptake of thiamine with reported K m values of ~2.5 and 27 nM, respectively. 39,40 To establish if SLC19A3 expression occurs after acute hypoxia exposure, cells were treated for up to 72 h in 1% O 2 or with DFO.…”

Role of thiamine in Huntington’s disease pathogenesis: In vitro studies

“…3.5-fold GPR) in the intact cells with mHTT towards control. 20 The increase in GAPDH and SLC19A3 transcripts level was shown also in B lymphocytes with mHTT upon thiamine deficit and upon supplementation with 1 mM of the vitamin, which is difficult to explain, especially in deficit conditions. mRNA of the genes which encode the thiamine-related enzymes and the other enzymes involved in energy metabolism in human B lymphocytes upon thiamine deficit and consequently upon thiamine supplementation was not changed.…”