代谢组学研究技术及应用 生物系 赵闯营
目 录 什么是代谢组学 ? 代谢组学主要研究技术 代谢组学应用举例
系 统 生 物 学 Gene一 mRNA— Protein— >> Metabolite
一、什么是代谢组学 • 1.代谢组学的提出 Jeremy K. Nicholson教授作为代谢组学的先行者，被誉为国际“代谢组学之父”. Metabonomics:the quantitative measurement of the multi-parametric metabolic response of living systems to pathophysiological stimuli or genetic modifications. 生物系统对生理和病理刺激以及基因改变的代谢应答的定量测定. • 2.代谢组学的概念 在现有的英文表述中，代谢组学同时存在两个不同的词汇和概念，即metabonomics和metabolomics.
Metabolomics存在多个定义，但其精髓是：对一个生物系统的细胞在给定时间和给定条件下所有小分子代谢物质的定量分析 (the quantitative measurement of all low molecular weight metabolites in an organism cells at a specified time under specific environmental conditions). Metabolomics着重研究的是单个细 胞或细胞类型中所有的小分子成分和波动规律,或许可以叫做细胞代谢组学. 多用于植物和微生物系统. • Metabonomics代谢组学是关于定量描述生物内源性代谢物质的整体及其对内因和外因变化应答规律的科学. (Metabonomics is the branch of science concerned with the quantitative understandings of the metabolite complement of integrated living systems and its dynamic responses to the changes of both endogenous factors (such as physiology and development) and exogenous factors (such as environmental factors and xenobiotics)). • 因此，Metabolomics可以译作代谢物组学.Metabolomics 是Metabonomics的一个组成部分.
Van De Greef:publication of MS for urine profiling 1982 Sadler, Buckingham and Nicholson:First publication on 1H-NMR of blood and plasma 1983 Nicholson, et al.: Multi-component analysis of spectra data from rat urine 1984 Nicholson and Wilson:NMR spectroscopy of biofluids 1989 Nicholson: Definition of Metabonomics 1999 Haselden, et al.:First independent Pharma publication of Metabonomics 2000 Nicholson, Lindon, and Holmes:Publication in Nature on Metabonomics 2001 Holmes and Antti Explanation of statistics in Metabonomics 2002 Increasing # of publications 2007 3.代谢组学的发展
Abstract Proton-NMR-based metabonomics offers a rare opportunity as a definitive screening technique for biofluids and tissue biopsies. The procedure is extraordinary in that it allows the ‘complete biochemical picture’ to be examined at one time and is able to detect subtle but repeatedly consistent disparities that may be occurring in different, and perhaps unrelated, biochemical pathways. Such metabolic responses to an initial perturbation in homeostasis may be followed over a sequential time-course to their eventual dissipation or consequent sequelae. The application of this technique is beginning slowly to filter into the area of endocrine research and has been used to examine long-term and diffuse physiological alterations that may occur following such events as anabolic steroid treatment of cattle and the exposure of endometrial cells to tamoxifen. Although only modest inroads have been made so far, this technique promises immense potential for future researches within the endocrine field.
Contents 1. Introduction 2. Proton nuclear magnetic resonance spectroscopy 3. The metabonomic approach and pattern recognition 4. Application within the biological field 5. Hormones, drugs and the endocrine system References
1. What is Metabonomics? Metabonomics:the quantitative measurement of the multi-parametric metabolic response of living systems to pathophysiological stimuli or genetic modifications. (生物系统对生理和病理刺激以及基因改变的代谢应答的定量测定) 2.Principle of proton-NMR 在特殊的磁场中，用无线电射频脉冲激发氢原子核，引起氢原子核共振，并吸收能量。在停止射频脉冲后，氢原子核按特定频率发出射电信号，并将吸收的能量释放出来，被体外的接受器收录，经电子计算机处理获得图像． 3. 1H-NMR and methods of analysis NMR data NLM HCA and PCA ……. unsupervised SIMCA NNs and PNNs ………supervised
4. Metabonomic approach in medical care 5.The immense potential of the metabonomic approach in the field of intermediary metabolism and endocrine control