Metabolite sensing is one of the most fundamental biological processes. During evolution, multilayered mechanisms developed to sense fluctuations in a wide spectrum of metabolites, including nutrients, to coordinate cellular metabolism and biological networks. To date, AMPK and mTOR signaling are among the best-understood metabolite-sensing and signaling pathways. Here, we propose a sensor-transducer-effector model to describe known mechanisms of metabolite sensing and signaling. We define a metabolite sensor by its specificity, dynamicity, and functionality. We group the actions of metabolite sensing into three different modes: metabolite sensor-mediated signaling, metabolite-sensing module, and sensing by conjugating. With these modes of action, we provide a systematic view of how cells sense sugars, lipids, amino acids, and metabolic intermediates. In the future perspective, we suggest a systematic screen of metabolite-sensing macromolecules, high-throughput discovery of biomacromolecule-metabolite interactomes, and functional metabolomics to advance our knowledge of metabolite sensing and signaling. Most importantly, targeting metabolite sensing holds great promise in therapeutic intervention of metabolic diseases and in improving healthy aging.

代谢物感测是最基本的生物学过程之一。在进化过程中，开发了多层机制来感知包括营养在内的多种代谢产物的波动，以协调细胞代谢和生物网络。迄今为止，AMPK和mTOR信号传导是最容易理解的代谢物感应和信号传导途径之一。在这里，我们提出了一种传感器-传感器-效应子模型来描述已知的代谢物传感和信号传导机制。我们通过其特异性，动态性和功能性来定义代谢物传感器。我们将代谢物传感的作用分为三种不同的模式：代谢物传感器介导的信号传导，代谢物传感模块和共轭传感。通过这些作用方式，我们可以系统地了解细胞如何感测糖，脂质，氨基酸，和代谢中间体。在未来的观点中，我们建议对代谢物敏感的大分子进行系统的筛选，高通量的生物大分子-代谢物相互作用组的发现以及功能代谢组学，以提高我们对代谢物传感和信号传导的了解。最重要的是，在代谢疾病的治疗干预和改善健康衰老方面，靶向代谢物检测具有广阔的前景。