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首页> 外文学位 >2-Hydrazinoquinoline as a novel derivatization agent for LC-MS-based metabolomic investigation of ketoacidosis in streptozotocin-elicited diabetes.
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2-Hydrazinoquinoline as a novel derivatization agent for LC-MS-based metabolomic investigation of ketoacidosis in streptozotocin-elicited diabetes.

机译：2-羟基喹啉是一种新型的衍生化试剂，用于基于链霉菌素引起的糖尿病的酮症酸中毒的基于LC-MS的代谢组学研究。

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摘要

Short-chain carboxylic acids, aldehydes, and ketones are important intermediates and end products of many metabolic processes. Their levels in biofluids and tissues can reflect the status of specific metabolic reactions, the homeostasis of whole metabolic system, and the well-being of a biological entity. Traditionally, GC-MS has been widely used for analyzing carboxylic acids, aldehydes, and ketones in biological samples after chemical derivatization. However, due to poor compatibility of common GC columns with water, the derivatization process in GC-MS is often complicated and time consuming, especially for the metabolites in biofluids and tissues. Recently, new chemical derivatization techniques have been developed to enhance the sensitivity and performance of LC-MS for analyzing these metabolites. In this study, the use of 2-hydrazinoquinoline (HQ) as a novel derivatization agent for LC-MS analysis of carboxylic acids, aldehydes, and ketones in biological samples was explored, and the conditions for the derivatization reaction were optimized. The metabolites in urine, serum, and tissue extracts can be conveniently derivatized in a 60-min process. The formation of carboxylic acid derivatives is attributed to the esterification reaction between HQ and carboxyl group, while the production of aldehyde and ketone derivatives is through the formation of Schiff bases between HQ and carbonyl group. Compared to other known hydrazine derivatization agents, including 2-hydrazinopyridine, 2-picolylamine and dansyl hydrazine, HQ can react with a broader spectrum of intermediary metabolites in biological samples, and can achieve better chromatographic performance in reversed phase LC system and higher ionization efficiency in electrospray source. Using this HQ-based approach, the metabolic disorder induced by streptozotocin-elicited diabetes was examined by the LC-MS-based metabolomics. The results showed the time-dependent separation of mouse urine samples from STZ treatment in a multivariate model of urinary metabolites. Both known and novel small-molecule biomarkers associated with STZ-induced ketoacidosis were conveniently identified and subsequently elucidated, reflecting the dramatic changes in nutrient (glucose, amino acid, and lipid) and energy metabolism after STZ treatment. Overall, HQ derivatization of carboxylic acids, aldehydes, and ketones can be an effective platform for the LC-MS-based metabolomic investigation of endogenous metabolism.
机译：短链羧酸，醛和酮是许多代谢过程的重要中间体和终产物。它们在生物流体和组织中的水平可以反映特定代谢反应的状态，整个代谢系统的稳态以及生物实体的健康状况。传统上，GC-MS已被广泛用于化学衍生化后的生物样品中羧酸，醛和酮的分析。但是，由于普通GC色谱柱与水的相容性差，GC-MS中的衍生化过程通常很复杂且耗时，特别是对于生物流体和组织中的代谢物。最近，已开发出新的化学衍生技术以增强LC-MS分析这些代谢物的灵敏度和性能。在这项研究中，探索了使用2-肼基喹啉（HQ）作为新型衍生化剂对生物样品中的羧酸，醛和酮进行LC-MS分析，并优化了衍生化反应的条件。尿液，血清和组织提取物中的代谢物可以在60分钟的过程中方便地衍生化。羧酸衍生物的形成归因于HQ和羧基之间的酯化反应，而醛和酮衍生物的产生是通过HQ和羰基之间的席夫碱的形成。与其他已知的肼衍生剂（包括2-肼基吡啶，2-甲基吡啶胺和丹磺酰肼）相比，HQ可以与生物样品中更广泛的中间代谢物发生反应，并且可以在反相LC系统中实现更好的色谱性能，并在更高的电离效率下电喷雾源。使用基于HQ的方法，通过基于LC-MS的代谢组学研究了链脲佐菌素诱发的糖尿病引起的代谢紊乱。结果显示，在尿液代谢产物的多变量模型中，从STZ处理的小鼠尿液样品的时间依赖性分离。与STZ诱导的酮症酸中毒相关的已知和新颖的小分子生物标记物都可以方便地鉴定并随后阐明，反映了STZ处理后营养素（葡萄糖，氨基酸和脂质）和能量代谢的显着变化。总体而言，羧酸，醛和酮的HQ衍生化可以成为基于LC-MS的内源代谢代谢组学研究的有效平台。

著录项

  • 作者

    Lu, Yuwei.;

  • 作者单位

    University of Minnesota.;

  • 授予单位 University of Minnesota.;
  • 学科 Health Sciences Nutrition.
  • 学位 M.S.
  • 年度 2013
  • 页码 97 p.
  • 总页数 97
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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