Shu Mincong, Liu Yuhan, Wang Jianbin
The Fifth Clinical School of Hubei University of Medicine, Shiyan, 442000, China.
College of Medicine, Jinggangshan University, Ji'an, 343000, China.
Cell Commun Signal. 2025 Jul 1;23(1):311. doi: 10.1186/s12964-025-02327-4.
Serine is a non-essential amino acid, serving as a precursor for other amino acids, lipids, and nucleotide synthesis. Its supply is ensured by two main mechanisms: exogenous uptake and endogenous synthesis. The serine synthesis pathway (SSP) connects glycolysis with the one-carbon cycle and plays an important role in cellular homeostasis by regulating substance synthesis, redox homeostasis, and gene expression. The de novo SSP involves three successive enzymatic reactions catalyzed by phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH). Post-translational modifications (PTMs), as essential regulatory mechanisms of proteins, play pivotal roles in physiological and pathological processes. This review focuses on the regulatory mode of PTMs on PHGDH, PSAT1, and PSPH, including phosphorylation, ubiquitination, acetylation, methylation, S-palmitoylation, S-nitrosylation, deamidation, SUMOylation, and lactylation. We summarize how these PTMs participate in the metabolic reprogramming of SSP. It helps us better understand the molecular mechanisms and physiological significance of the PTM network in serine synthetic metabolism, providing guidance for subsequent research and development in the future.
丝氨酸是一种非必需氨基酸，是其他氨基酸、脂质和核苷酸合成的前体。其供应通过两种主要机制来确保：外源性摄取和内源性合成。丝氨酸合成途径（SSP）将糖酵解与一碳循环联系起来，并通过调节物质合成、氧化还原稳态和基因表达在细胞稳态中发挥重要作用。从头合成SSP涉及由磷酸甘油酸脱氢酶（PHGDH）、磷酸丝氨酸氨基转移酶1（PSAT1）和磷酸丝氨酸磷酸酶（PSPH）催化的三个连续酶促反应。翻译后修饰（PTM）作为蛋白质的重要调节机制，在生理和病理过程中起关键作用。本综述重点关注PTM对PHGDH、PSAT1和PSPH的调节模式，包括磷酸化、泛素化、乙酰化、甲基化、S-棕榈酰化、S-亚硝基化、脱酰胺化、SUMO化和乳酸化。我们总结了这些PTM如何参与SSP的代谢重编程。这有助于我们更好地理解丝氨酸合成代谢中PTM网络的分子机制和生理意义，为未来的后续研究和开发提供指导。
