Riboflavin Transporters RFVT/SLC52A Mediate Translocation of Riboflavin, Rather than FMN or FAD, across Plasma Membrane

Riboflavin Transporters RFVT/SLC52A Mediate Translocation of Riboflavin, Rather than FMN or FAD, across Plasma Membrane
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DOI:
10.1248/bpb.b17-00292
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发表时间:
2017-11-01
影响因子:
2
通讯作者:
Matsubara, Kazuo
Matsubara, Kazuo
中科院分区:
医学4区
文献类型:
--
作者:
Jin, Congyun;Yao, Yoshiaki;Matsubara, Kazuo

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核黄素(维生素B2)在多种生化氧化还原反应中起作用。黄素单核苷酸(FMN)和FAD是由核黄素合成的生物活性形式。核黄素转运体(rfvt) RFVT1-31Slc52a1-3已被鉴定。然而,人类(h)RFVTs在FMN和FAD稳态中的作用尚未完全阐明。在这项研究中,我们通过体外研究评估了每种hRFVT对核黄素、FMN和FAD摄取和排出的贡献。转染hrfvt增加细胞核黄素浓度。转染hrfvt的人胚胎肾细胞对核黄素的摄取显著增加,并且以时间依赖性的方式加速外排。然而,FMN和FAD的摄取和排出几乎没有变化。这些结果强烈提示核黄素,而不是FMN或FAD,通过hrfvt通过质膜。我们的研究结果表明,hrfvt参与细胞内核黄素稳态,FMN和FAD浓度受核黄素激酶和FAD合成酶的调节。
Riboflavin (vitamin B2) plays a role in various biochemical oxidation-reduction reactions. Flavin mono nucleotide (FMN) and FAD, the biologically active forms, are made from riboflavin. Riboflavin transporters (RFVTs), RFVT1-31Slc52a1-3, have been identified. However, the roles of human (h)RFVTs in FMN and FAD homeostasis have not yet been fully clarified. In this study, we assessed the contribution of each hRFVT to riboflavin, FMN and FAD uptake and efflux using in vitro studies. The transfection of hRFVTs increased cellular riboflavin concentrations. The uptake of riboflavin by human embryonic kidney cells transfected with hRFVTs was significantly increased, and the efflux was accelerated in a time-dependent manner. However, the uptake and efflux of FMN and FAD hardly changed. These results strongly suggest that riboflavin, rather than FMN or FAD, passes through plasma membranes via hRFVTs. Our findings could suggest that hRFVTs are involved in riboflavin homeostasis in the cells, and that FMN and FAD concentrations are regulated by riboflavin kinase and FAD synthase.