对代谢组学的含义,中心任务,研究方法,样品要求,应用及其发展方向进行了简要综述. 系统生物学概念的诞生标志着研究哲学由“还原论”向“整体论”的变化. 系统生物学的中心任务就是要针对生物系统整体 (无论它是生物细胞,多细胞组织,器官还是生物整体),建立定量,普适,整体和可预测 (QUIP) 的认知. 具体而言,系统生物学研究就是要将给定生物系统的基因,转录,蛋白质和代谢水平所发生的事件,相关性及其对所涉及生物过程的意义进行整体性认识. 从而出现了许多的“组”和“组学”的新概念. 但是现已提出的一百多个“组”和“组学”,可以大体归纳为“基因组”/“基因组学”,“转录组”/“转录组学”,“蛋白质组”/“蛋白质组学”和“代谢组”/“代谢组学”四个方面. 显而易见,DNA,mRNA 以及蛋白质的存在为生物过程的发生提供了物质基础 (但这个过程有可能不发生!),而代谢物质所反映的是已经发生了的生物学事件. 因此代谢组学是对一个生物系统进行全面认识的不可缺少的一部分,是全局系统生物学 (global systems biology) 的重要基础,也是系统生物学的一个重要组成部分. 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. 尽管前者多用在动物系统而后者多用于植物和微生物系统,但这些概念的本质从他们的定义中能够得到较细致的了解. Metabonomics 的最初定义是就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(“the quantitative measurement of the multi-parametric metabolic response of living systems to pathophysiological stimuli or geneticmodifications”). 我们认为这个定义现在可以更广泛地表述为: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 s
Clinical data have shown that survival rates vary considerably among brain tumor patients,according to the type and grade of the tumor.Metabolite profiles of intact tumor tissues measured with high-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy (HRMAS 1H NMRS) can provide important information on tumor biology and metabolism.These metabolic fingerprints can then be used for tumor classification and grading,with great potential value for tumor diagnosis.We studied the metabolic characteristics of 30 neuroepithelial tumor biopsies,including two astrocytomas (grade I),12 astrocytomas (grade II),eight anaplastic astrocytomas (grade III),three glioblastomas (grade IV) and five medulloblastomas (grade IV) from 30 patients using HRMAS 1H NMRS.The results were correlated with pathological features using multivariate data analysis,including principal component analysis (PCA).There were significant differences in the levels of N-acetyl-aspartate (NAA),creatine,myo-inositol,glycine and lactate between tumors of different grades (P<0.05).There were also significant differences in the ratios of NAA/creatine,lactate/creatine,myo-inositol/creatine,glycine/creatine,scyllo-inositol/creatine and alanine/creatine (P<0.05).A soft independent modeling of class analogy model produced a predictive accuracy of 87% for high-grade (grade III-IV) brain tumors with a sensitivity of 87% and a specificity of 93%.HRMAS 1H NMR spectroscopy in conjunction with pattern recognition thus provides a potentially useful tool for the rapid and accurate classification of human brain tumor grades.
利用固相萃取分离和核磁共振技术(nuclear magnetic resonance,NMR)对人体尿液中的代谢物进行了较为系统的研究.通过对人体尿液样品固相萃取后分离得到的五个组分1HNMR,同核二维氢谱(correlation spectroscopy,COSY)和全相关谱(total correlation spectroscopy,TOCSY),异核相关光谱(heteronuclear single quantum correlation,HSQC和Heteronuclear muptiple bond correlation,HMBC),J-分解谱(J-resolvedspectroscopic,J-RES)的谱图分析,解析出了74种化合物的1H和13C化学位移,并对一维1H谱的多数谱峰进行了有效指认.
Nuclear magnetic resonance (NMR) spectroscopic analysis of metabonome/metabolome has widespread applications in biomedical science researches. However, most of NMR resonances for urinary metabolites remain to be fully assigned. In the present study, human urine samples from two healthy volunteers were pre-treated with C18 solid-phase extraction and the resultant 5 sub-fractions were subjected to one- and two-dimensional NMR studies, including 1H J-Resolved, 1H-1H COSY, 1H-1H TOCSY, 1H-13C HSQC, and HMBC 2D NMR. More than 70 low molecular weight metabolites were identified, and complete assignments of 1H and 13C resonances including many complex coupled spin systems were obtained.
