Departments of Microbiology, Immunology, and Molecular Genetics,
Molecular and Medical Pharmacology,Crump Institute for Molecular Imaging.
Proc Natl Acad Sci U S A. 2014 Jul 15;111(28):E2866-74. doi: 10.1073/pnas.1410326111. Epub 2014 Jun 30.
PET is a powerful technique for quantifying and visualizing biochemical pathways in vivo. Here, we develop and validate a novel PET probe, [(18)F]-2-deoxy-2-fluoroarabinose ([(18)F]DFA), for in vivo imaging of ribose salvage. DFA mimics ribose in vivo and accumulates in cells following phosphorylation by ribokinase and further metabolism by transketolase. We use [(18)F]DFA to show that ribose preferentially accumulates in the liver, suggesting a striking tissue specificity for ribose metabolism. We demonstrate that solute carrier family 2, member 2 (also known as GLUT2), a glucose transporter expressed in the liver, is one ribose transporter, but we do not know if others exist. [(18)F]DFA accumulation is attenuated in several mouse models of metabolic syndrome, suggesting an association between ribose salvage and glucose and lipid metabolism. These results describe a tool for studying ribose salvage and suggest that plasma ribose is preferentially metabolized in the liver.
PET 是一种强大的技术，可用于定量和可视化体内的生化途径。在这里，我们开发并验证了一种新型的 PET 探针，[(18)F]-2-脱氧-2-氟阿拉伯糖([(18)F]DFA)，用于核糖补救的体内成像。DFA 在体内模拟核糖，并在被核糖激酶磷酸化后通过转酮醇酶进一步代谢而在细胞中积累。我们使用[(18)F]DFA 表明，核糖优先在肝脏中积累，这表明核糖代谢具有惊人的组织特异性。我们证明溶质载体家族 2，成员 2(也称为 GLUT2)，一种在肝脏中表达的葡萄糖转运蛋白，是一种核糖转运蛋白，但我们不知道是否存在其他的。[(18)F]DFA 的积累在几种代谢综合征的小鼠模型中被减弱，这表明核糖补救与葡萄糖和脂质代谢之间存在关联。这些结果描述了一种研究核糖补救的工具，并表明血浆核糖优先在肝脏中代谢。
