Metabolism is the collection of biochemical reactions enabled by chemically diverse metabolites, which facilitate different physiological processes to exchange substances and synthesize energy in diverse living organisms. Metabolomics has emerged as a cutting‐edge method to qualify and quantify the metabolites in different biological matrixes, and it has the extraordinary capacity to interrogate the biological significance that underlies metabolic modification and modulation. Liquid chromatography combined with mass spectrometry (LC/MS), as a robust platform for metabolomics analysis, has increased in popularity over the past 10 years due to its excellent sensitivity, throughput, and versatility. However, metabolomics investigation currently provides us with only phenotype data without revealing the biochemical functions and associated mechanisms. This limitation indeed weakens the core value of metabolomics data in a broad spectrum of the life sciences. In recent years, the scientific community has actively explored the functional features of metabolomics and translated this cutting‐edge approach to be used to solve key multifaceted questions, such as disease pathogenesis, the therapeutic discovery of drugs, nutritional issues, agricultural problems, environmental toxicology, and microbial evolution. Here, we are the first to briefly review the history and applicable progression of LC/MS‐based metabolomics, with an emphasis on the applications of metabolic phenotyping. Furthermore, we specifically highlight the next era of LC/MS‐based metabolomics to target functional metabolomes, through which we can answer phenotype‐related questions to elucidate biochemical functions and associated mechanisms implicated in dysregulated metabolism. Finally, we propose many strategies to enhance the research capacity of functional metabolomics by enabling the combination of contemporary omics technologies and cutting‐edge biochemical techniques. The main purpose of this review is to improve the understanding of LC/MS‐based metabolomics, extending beyond the conventional metabolic phenotype toward biochemical functions and associated mechanisms, to enhance research capability and to enlarge the applicable scope of functional metabolomics in small‐molecule metabolism in different living organisms.

中文翻译：

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功能代谢组学决定了小分子代谢的生物化学功能和相关机制。

代谢是由化学上多样化的代谢物促成的生化反应的集合，这些代谢物促进不同的生理过程在不同的生物体中交换物质和合成能量。代谢组学已成为对不同生物基质中的代谢物进行定性和量化的前沿方法，它具有研究代谢修饰和调节背后的生物学意义的非凡能力。液相色谱结合质谱 (LC/MS) 作为代谢组学分析的强大平台，由于其出色的灵敏度、通量和多功能性，在过去 10 年中越来越受欢迎。然而，代谢组学研究目前仅为我们提供表型数据，而没有揭示生化功能和相关机制。这种限制确实削弱了代谢组学数据在广泛的生命科学领域的核心价值。近年来，科学界积极探索代谢组学的功能特征，并将这种前沿方法用于解决多方面的关键问题，如疾病发病机制、药物治疗发现、营养问题、农业问题、环境毒理学。和微生物进化。在这里，我们首先简要回顾了基于 LC/MS 的代谢组学的历史和适用进展，重点是代谢表型的应用。此外，我们特别强调了基于 LC/MS 的代谢组学的下一个时代，以靶向功能代谢组，通过它我们可以回答与表型相关的问题，以阐明与代谢失调有关的生化功能和相关机制。最后，我们提出了许多策略，通过结合当代组学技术和尖端生化技术来提高功能代谢组学的研究能力。本综述的主要目的是提高对基于 LC/MS 的代谢组学的理解，从传统的代谢表型扩展到生化功能和相关机制，增强研究能力并扩大功能代谢组学在小分子代谢中的适用范围。在不同的生物体中。我们提出了许多策略，通过结合当代组学技术和尖端生化技术来提高功能代谢组学的研究能力。本综述的主要目的是提高对基于 LC/MS 的代谢组学的理解，从传统的代谢表型扩展到生化功能和相关机制，增强研究能力并扩大功能代谢组学在小分子代谢中的适用范围。在不同的生物体中。我们提出了许多策略，通过结合当代组学技术和尖端生化技术来提高功能代谢组学的研究能力。本综述的主要目的是提高对基于 LC/MS 的代谢组学的理解，从传统的代谢表型扩展到生化功能和相关机制，增强研究能力并扩大功能代谢组学在小分子代谢中的适用范围。在不同的生物体中。