Jin Congyun, Yao Yoshiaki, Yonezawa Atsushi, Imai Satoshi, Yoshimatsu Hiroki, Otani Yuki, Omura Tomohiro, Nakagawa Shunsaku, Nakagawa Takayuki, Matsubara Kazuo
Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital.
Biol Pharm Bull. 2017;40(11):1990-1995. doi: 10.1248/bpb.b17-00292.
Riboflavin (vitamin B2) plays a role in various biochemical oxidation-reduction reactions. Flavin mononucleotide (FMN) and FAD, the biologically active forms, are made from riboflavin. Riboflavin transporters (RFVTs), RFVT1-3/Slc52a1-3, 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.
核黄素（维生素B2）在各种生物化学氧化还原反应中发挥作用。黄素单核苷酸（FMN）和黄素腺嘌呤二核苷酸（FAD）这两种生物活性形式由核黄素生成。已鉴定出核黄素转运体（RFVTs），即RFVT1 - 3/Slc52a1 - 3。然而，人类（h）RFVTs在FMN和FAD体内平衡中的作用尚未完全阐明。在本研究中，我们通过体外研究评估了每种hRFVT对核黄素、FMN和FAD摄取及外排的贡献。hRFVTs的转染增加了细胞内核黄素浓度。用hRFVTs转染的人胚肾细胞对核黄素的摄取显著增加，且外排呈时间依赖性加速。然而，FMN和FAD的摄取及外排几乎没有变化。这些结果有力地表明，核黄素而非FMN或FAD通过hRFVTs穿过质膜。我们的研究结果可能表明，hRFVTs参与细胞内核黄素的体内平衡，且FMN和FAD的浓度由核黄素激酶和FAD合酶调节。
