Mayr Manuel
Cardiovascular Division, King's College, London School of Medicine, King's College London, UK.
Circ Cardiovasc Genet. 2008 Oct;1(1):58-65. doi: 10.1161/CIRCGENETICS.108.808329.
Metabolomics is one of the most rapidly growing areas of contemporary science. Although classic genetics aims to link variations in the DNA sequence directly to distinct phenotypes, "-omic" technologies allow us to shift the focus from the specific gene to the actual effects of the gene itself. Because neither the transcriptional or protein profile can be directly correlated with metabolite concentrations, the importance of measuring small-molecule metabolites has become increasingly clear. In view of the rapid progress in metabolomic techniques, metabolomics is expected to become more widely applied to cardiovascular research. Metabolomics brings the promise of the identification of potential biomarkers and alterations in biochemical pathways, which will facilitate the transition from a reductionistic approach to a more integrated science. Because the relative lack of attention given to the system behavior hampers our progress in translating basic science research into clinical applications,the holistic nature of these emerging techniques may yield valuable new strategies for the prevention and treatment of cardiovascular diseases. By analogy to the genome, the metabolome is defined as the total complement of small-molecule metabolites found in or produced by an organism. The most recent estimates place the number of endogenous metabolites (metabolites synthesized by enzymes encoded in the human genome) at approximately a few thousand, far less than had been previously predicted. Importantly, the size of the exogenous metabolome(metabolites not synthesized in the body but consumed as food or generated by host-specific microbes) is far greater,and there is often a spatial separation between metabolite synthesis and use. Hence, although genes, proteins, and metabolites are intimately connected in biological systems and their interactions with environmental changes are reflected in the metabolome, gene or protein expression may not directly correlate to metabolite concentrations from the same region (Figure 1). Thus, there is a clear need for an additional readout at the metabolite level, and the promise of "metabolomic profiling" is to achieve a quantitative and qualitative assessment of a subset of metabolites in complex samples such as bodily fluids and tissues.
代谢组学是当代科学中发展最为迅速的领域之一。虽然经典遗传学旨在将DNA序列的变异直接与不同的表型联系起来，但“组学”技术使我们能够将重点从特定基因转移到基因本身的实际效应上。由于转录谱或蛋白质谱都不能直接与代谢物浓度相关联，测量小分子代谢物的重要性日益凸显。鉴于代谢组学技术的快速发展，代谢组学有望更广泛地应用于心血管研究。代谢组学有望识别潜在的生物标志物并揭示生化途径的改变，这将有助于从还原论方法向更综合的科学转变。由于对系统行为相对缺乏关注阻碍了我们将基础科学研究转化为临床应用的进程，这些新兴技术的整体性可能会为心血管疾病的预防和治疗带来有价值的新策略。类似于基因组，代谢组被定义为生物体中发现的或由生物体产生的小分子代谢物的总和。最新估计显示，内源性代谢物（由人类基因组编码的酶合成的代谢物）的数量约为几千种，远少于先前的预测。重要的是，外源性代谢组（非体内合成但作为食物消耗或由宿主特异性微生物产生的代谢物）的规模要大得多，而且代谢物的合成与使用之间往往存在空间分离。因此，尽管基因、蛋白质和代谢物在生物系统中密切相关，并且它们与环境变化的相互作用反映在代谢组中，但基因或蛋白质表达可能与同一区域的代谢物浓度没有直接关联（图1）。因此，显然需要在代谢物水平进行额外的读数，而“代谢组学分析 ”的前景是对体液和组织等复杂样品中的一部分代谢物进行定量和定性评估。
