Vitamin C metabolomic mapping in experimental diabetes with 6-deoxy-6-fluoro-ascorbic acid and high resolution 19F-nuclear magnetic resonance spectroscopy
Vitamin C metabolomic mapping in experimental diabetes with 6-deoxy-6-fluoro-ascorbic acid and high resolution 19F-nuclear magnetic resonance spectroscopy
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DOI：
10.1016/s0026-0495(03)00069-6
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发表时间：
2003-06-01
影响因子：
9.8
通讯作者：
Monnier, VM
中科院分区：
文献类型：
--
作者：
Nishikawa, Y;Dmochowska, B;Monnier, VM
代谢组学图谱是一门新兴学科，旨在提供大量代谢物的信息，作为基因组学和蛋白质组学的补充。在这里，我们已经探测抗坏血酸稳态和降解糖尿病使用6-脱氧-6-氟抗坏血酸（F-ASA）和750 MHz F-19-核磁共振（NMR）光谱与质子去耦在体外，Cu 2+介导的降解F-ASA显示4个主要的稳定降解产物的形成在24小时。然而，当正常或糖尿病大鼠腹腔注射F-ASA（IP）4天后，在尿液中观察到多达20种氟标记化合物。其组成部分类似于F-ASA的金属催化降解，不能通过尿液中的自发降解来解释。糖尿病导致尿中F-ASA损失急剧增加，而大多数其他尿中F-化合物相对减少。糖尿病使肝脏（P <0.01）、肾脏（P <0.01）、脾脏（P <0.01）和血浆（P <0.01）中的F-ASA稳态向氧化方向倾斜，但倾向于降低大脑、肾上腺和心脏的氧化。然而，令人惊讶的是，除了主要的氧化产物氟脱氢抗坏血酸（F-DHA），在5 μ mol/L的灵敏度下，在组织中没有检测到F-ASA晚期catalysts。这些发现不仅证实了肾脏在糖尿病介导的抗坏血酸损失中的关键作用，而且表明只有选定的组织易于在糖尿病中增加氧化。虽然大多数降解产物的结构需要建立，但该方法说明了高分辨率F-19-NMR光谱在疾病状态下绘制复杂代谢途径的能力。(C)2003年爱思唯尔公司All rights reserved.
Metabolomic mapping is an emerging discipline geared at providing information on a large number of metabolites as a complement to genomics and proteomics. Here we have probed ascorbic acid homeostasis and degradation in diabetes using 6-deoxy-6-fluoro ascorbic acid (F-ASA) and 750 MHz F-19-nuclear magnetic resonance (NMR) spectroscopy with proton decoupling In vitro, Cu2+-mediated degradation of F-ASA revealed the formation of 4 major stable degradation products at 24 hours. However, when normal or diabetics rats were injected with F-ASA intraperitoneally (IP) for 4 days, up to 20 fluorine-labeled compounds were observed in the urine. Their composition resembled, in part, metal catalyzed degradation of F-ASA and was not explained by spontaneous degradation in the urine. Diabetes led to a dramatic increase in urinary F-ASA loss and a relative decrease in most other urinary F-compounds. Diabetes tilted F-ASA homeostasis toward oxidation in liver [P < .01), kidney (P < .01), spleen (P < .01), and plasma (P < .01), but tended to decrease oxidation in brain, adrenal glands, and heart. Surprisingly, however, besides the major oxidation product fluoro-dehydroascorbic acid (F-DHA), no F-ASA advanced catabolites were detected in tissues at 5 mu mol/L sensitivity. These findings not only confirm the key role of the kidney in diabetes-mediated loss of ascorbic acid, but demonstrate that only selected tissues are prone to increased oxidation in diabetes. While the structure of most degradation products needs to be established, the method illustrates the power of high resolution F-19-NMR spectroscopy for the mapping of complex metabolomic pathways in disease states. (C) 2003 Elsevier Inc. All rights reserved.