色谱 ›› 2015, Vol. 33 ›› Issue (2): 112-115.DOI: 10.3724/SP.J.1123.2014.11011

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同位素示踪技术定量分析肿瘤细胞中的代谢重编

林树海, 蔡宗苇   

  1. 香港浸会大学化学系, 环境与生物分析国家重点实验室, 香港 999077
  • 收稿日期:2014-11-10 修回日期:2014-12-09 出版日期:2015-02-08 发布日期:2015-01-24
  • 通讯作者: 蔡宗苇, 林树海
  • 基金资助:

    国家自然科学基金资助项目(21377106).

Isotopic tracing technique in quantitative analysis of metabolic reprogramming in tumor cells

LIN Shuhai, CAI Zongwei   

  1. Department of Chemistry, Hong Kong Baptist University, State Key Laboratory of Environmental and Biological Analysis, Hong Kong 999077, China
  • Received:2014-11-10 Revised:2014-12-09 Online:2015-02-08 Published:2015-01-24

摘要:

肿瘤代谢在最近几年重新获得重视,讨论肿瘤代谢我们无法避开瓦伯格效应,尽管瓦伯格效应在20世纪20年代就提出来了。瓦伯格效应也称需氧糖酵解,是指在有氧的条件下癌细胞过量摄取葡萄糖,产生更多的乳酸。此外,癌细胞也可摄取其他物质,如谷氨酰胺、丝氨酸和甘氨酸等作为能量需求与营养来源。为了描述癌细胞中改变了的代谢通路,同位素标记示踪技术提供了一种新的全局观点,让我们更好地理解在癌基因或抑癌基因调控下的代谢切换。色谱与质谱联用是一种重要的分析工具,可定量检测带有同位素标记的代谢物,从而剖析肿瘤细胞中的生物化学反应。在本文中,我们总结了基于质谱的肿瘤代谢分析的研究概况并提出未来的研究方向。重点讨论碳-13标记与氘代标记的示踪技术分析中间代谢产物,包括还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)。目前生物化学教科书中认为NADPH主要来源于磷酸戊糖途径。然而,氘代示踪技术分析表明,包括一碳代谢在内的其他代谢通路对产生NADPH也很重要。以上内容都在本文中进行了讨论。

关键词: 代谢流分析, 同位素示踪, 细胞代谢, 质谱, 综述

Abstract:

It is hard to begin to discuss tumor metabolism without mentioning Warburg effect. Tumor metabolism has been received intensive attention in recent years for understanding Warburg effect which is also known as aerobic glycolysis. Even Warburg did not anticipate, other nutrients, such as glutamine, serine and glycine could serve as alternative source for energy demands and block building in cancer cells. To delineate altered metabolic pathways in cancer cells, isotopic tracing technique provides a novel and holistic insight in metabolic switch under control of oncogenes and tumor suppressor genes. An array of chromatography coupled with mass spectrometry is the powerful tool to detect the isotope-labeled metabolites for unlocking the underlying biochemical reactions in cancer cells. In this review article, we focus on carbon-13 and deuterium-labeling for quantitative analysis of intermediate metabolites including reduced form of nicotinamide adenine dinucleotide phosphate (NADPH). NADPH is mainly derived from pentose phosphate pathway in previous biochemical textbook. However, deuterium-isotope labeling metabolic flux analysis can reveal other important pathways for NADPH production, such as one-carbon metabolism, which is also discussed in this review.

Key words: cellular metabolism, isotopic tracing, mass spectrometry (MS), metabolic flux analysis, review

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