LC-NMR identification of a novel taurine-related metabolite observed in 1H NMR-based metabonomics of genetically hypertensive rats
LC-NMR identification of a novel taurine-related metabolite observed in 1H NMR-based metabonomics of genetically hypertensive rats
复制标题
DOI：
10.1016/j.jpba.2009.11.006
复制
发表时间：
2010-04-06
影响因子：
3.4
通讯作者：
Hashimoto, Takao
中科院分区：
文献类型：
--
作者：
Akira, Kazuki;Mitome, Hidemichi;Hashimoto, Takao
本文描述了一种负责信号的新型尿内源性代谢物的 LC-NMR 光谱鉴定，在之前基于 NMR 的代谢组学研究中，发现这种代谢物是区分遗传性高血压大鼠 (SHRSP) 和正常血压对照大鼠 (WKY) 的主要因素。采用配备对极性化合物具有高保留能力的反相柱的 LC-NMR 系统对 26 周龄正常血压大鼠的尿液样本进行了分析。在流动模式下连续获得 H-1 NMR 谱，并确定所讨论的未指定信号的保留时间。随后在停流模式下测量了包含未分配信号的部分的各种二维光谱，这使得能够长时间积累，从而提高信噪比。合成从这些LC-NMR数据获得的候选化合物，并将NMR和质谱与LC-NMR级分的NMR和质谱进行比较。从这些实验以及标准添加实验中，未知的代谢物被鉴定为琥珀酰牛磺酸。这种新的代谢物是正常血压大鼠的特征，非常有趣，因为它在结构上与低血压牛磺酸相关，并且在遗传性高血压大鼠中基本上未检测到，而遗传性高血压大鼠比正常血压大鼠分泌更多的牛磺酸。琥珀酰牛磺酸的生物学和病理生理学意义仍有待研究。 (C) 2009 Elsevier B.V. 保留所有权利。
This paper describes the LC-NMR spectroscopic identification of a novel urinary endogenous metabolite responsible for the signals, which were found as major contributors to the separation between genetically hypertensive rats (SHRSP) and normotensive control rats (WKY) in previous NMR-based metabonomic studies. Urine samples from 26-week-old normotensive rats were analyzed by an LC-NMR system equipped with a reversed-phase column having high retention ability for polar compounds. H-1 NMR spectra were continuously obtained in the on-flow mode, and the retention times of the unassigned signals in question were determined. Various two-dimensional spectra were subsequently measured for the fraction containing the unassigned signals under the stop-flow mode, which enables for a long accumulation resulting in the enhancement of signal-to-noise ratios. The candidate compound obtained from these LC-NMR data was synthesized, and the NMR and mass spectra were compared with those of the LC-NMR fraction. The unknown metabolite was identified as succinyltaurine from these experiments together with standard addition experiments. This novel metabolite, which is characteristic of the normotensive rats, is very interesting because it is structurally related to hypotensive taurine, and not substantially detected in the genetically hypertensive rats, which excreted more taurine than the normotensive rats. The biological and pathophysiological significances of succinyltaurine remain to be investigated. (C) 2009 Elsevier B.V. All rights reserved.