Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, USA.
Division of Veterinary Research, National Institutes of Health, USA.
EBioMedicine. 2017 Sep;23:125-135. doi: 10.1016/j.ebiom.2017.08.017. Epub 2017 Aug 22.
Despite its transport by glucose transporters (GLUTs) in vitro, it is unknown whether dehydroascorbic acid (oxidized vitamin C, DHA) has any in vivo function. To investigate, we created a chemical transport knockout model using the vitamin C analog 6-bromo-ascorbate. This analog is transported on sodium-dependent vitamin C transporters but its oxidized form, 6-bromo-dehydroascorbic acid, is not transported by GLUTs. Mice (gulo) unable to synthesize ascorbate (vitamin C) were raised on 6-bromo-ascorbate. Despite normal survival, centrifugation of blood produced hemolysis secondary to near absence of red blood cell (RBC) ascorbate/6-bromo-ascorbate. Key findings with clinical implications were that RBCs in vitro transported dehydroascorbic acid but not bromo-dehydroascorbic acid; RBC ascorbate in vivo was obtained only via DHA transport; ascorbate via DHA transport in vivo was necessary for RBC structural integrity; and internal RBC ascorbate was essential to maintain ascorbate plasma concentrations in vitro/in vivo.
尽管其在体外可通过葡萄糖转运蛋白（GLUTs）转运，但尚不清楚脱氢抗坏血酸（氧化型维生素 C，DHA）是否具有任何体内功能。为了研究这一问题，我们使用维生素 C 类似物 6-溴抗坏血酸创建了一种化学转运体敲除模型。该类似物可通过钠依赖性维生素 C 转运蛋白转运，但氧化形式 6-溴-脱氢抗坏血酸不能通过 GLUTs 转运。不能合成抗坏血酸（维生素 C）的小鼠（gulo）在 6-溴抗坏血酸上生长。尽管能够正常存活，但由于红细胞（RBC）中抗坏血酸/6-溴抗坏血酸几乎不存在，离心血液会导致溶血。具有临床意义的主要发现是 RBC 可在体外转运脱氢抗坏血酸但不能转运溴代脱氢抗坏血酸；体内 RBC 抗坏血酸只能通过 DHA 转运获得；体内通过 DHA 转运的抗坏血酸对 RBC 结构完整性是必需的；并且内部 RBC 抗坏血酸对于维持体外/体内抗坏血酸血浆浓度是必需的。
