Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
Amino Acids. 2021 Dec;53(12):1779-1788. doi: 10.1007/s00726-021-03051-2. Epub 2021 Jul 22.
Proline is a non-essential amino acid with key roles in protein structure/function and maintenance of cellular redox homeostasis. It is available from dietary sources, generated de novo within cells, and released from protein structures; a noteworthy source being collagen. Its catabolism within cells can generate ATP and reactive oxygen species (ROS). Recent findings suggest that proline biosynthesis and catabolism are essential processes in disease; not only due to the role in new protein synthesis as part of pathogenic processes but also due to the impact of proline metabolism on the wider metabolic network through its significant role in redox homeostasis. This is particularly clear in cancer proliferation and metastatic outgrowth. Nevertheless, the precise identity of the drivers of cellular proline catabolism and biosynthesis, and the overall cost of maintaining appropriate balance is not currently known. In this review, we explore the major drivers of proline availability and consumption at a local and systemic level with a focus on cancer. Unraveling the main factors influencing proline metabolism in normal physiology and disease will shed light on new effective treatment strategies.
脯氨酸是一种非必需氨基酸，在蛋白质结构/功能和维持细胞氧化还原稳态方面具有关键作用。它可以从饮食来源中获得，在细胞内从头生成，并从蛋白质结构中释放；胶原蛋白就是一个值得注意的来源。细胞内的脯氨酸分解代谢可以产生 ATP 和活性氧（ROS）。最近的研究结果表明，脯氨酸的生物合成和分解代谢是疾病中的重要过程；不仅因为它在新蛋白质合成中的作用是发病过程的一部分，还因为脯氨酸代谢通过其在氧化还原稳态中的重要作用对更广泛的代谢网络产生影响。在癌症增殖和转移生长中尤为明显。然而，目前尚不清楚细胞内脯氨酸分解代谢和生物合成的驱动因素以及维持适当平衡的总体成本。在这篇综述中，我们探讨了局部和全身水平脯氨酸可用性和消耗的主要驱动因素，重点是癌症。阐明影响正常生理和疾病中脯氨酸代谢的主要因素将为新的有效治疗策略提供启示。
