Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong 226001, China.
Research Center for Animal Husbandry, National Research and Innovation Agency, Jakarta Pusat 10340, Indonesia.
Int J Biol Macromol. 2024 Mar;260(Pt 2):129607. doi: 10.1016/j.ijbiomac.2024.129607. Epub 2024 Jan 20.
Serine is a metabolite with ever-expanding metabolic and non-metabolic signaling attributes. By providing one‑carbon units for macromolecule biosynthesis and functional modifications, serine and serine metabolism largely impinge on cellular survival and function. Cancer cells frequently have a preference for serine metabolic reprogramming to create a conducive metabolic state for survival and aggressiveness, making intervention of cancer-associated rewiring of serine metabolism a promising therapeutic strategy for cancer treatment. Beyond providing methyl donors for methylation in modulation of innate immunity, serine metabolism generates formyl donors for mitochondrial tRNA formylation which is required for mitochondrial function. Interestingly, fully developed neurons lack the machinery for serine biosynthesis and rely heavily on astrocytic l-serine for production of d-serine to shape synaptic plasticity. Here, we recapitulate recent discoveries that address the medical significance of serine and serine metabolism in malignancies, mitochondrial-associated disorders, and neurodegenerative pathologies. Metabolic control and epigenetic- and posttranslational regulation of serine metabolism are also discussed. Given the metabolic similarities between cancer cells, neurons and germ cells, we further propose the relevance of serine metabolism in testicular homeostasis. Our work provides valuable hints for future investigations that will lead to a deeper understanding of serine and serine metabolism in cellular physiology and pathology.
丝氨酸是一种具有不断扩大的代谢和非代谢信号属性的代谢物。通过为大分子生物合成和功能修饰提供一碳单位，丝氨酸和丝氨酸代谢在很大程度上影响细胞的存活和功能。癌细胞经常偏好丝氨酸代谢重编程，以创造有利于存活和侵袭的代谢状态，因此干预与癌症相关的丝氨酸代谢重编程是癌症治疗的一种有前途的治疗策略。除了为先天免疫的甲基化提供甲基供体外，丝氨酸代谢还产生甲酰供体，用于线粒体 tRNA 甲酰化，这是线粒体功能所必需的。有趣的是，完全发育的神经元缺乏丝氨酸生物合成的机制，严重依赖星形胶质细胞的 l-丝氨酸来产生 d-丝氨酸，以形成突触可塑性。在这里，我们总结了最近的发现，这些发现解决了丝氨酸和丝氨酸代谢在恶性肿瘤、线粒体相关疾病和神经退行性病理中的医学意义。丝氨酸代谢的代谢控制和表观遗传及翻译后调控也进行了讨论。鉴于癌细胞、神经元和生殖细胞之间的代谢相似性，我们进一步提出了丝氨酸代谢在睾丸稳态中的相关性。我们的工作为未来的研究提供了有价值的线索，这些研究将加深我们对细胞生理学和病理学中丝氨酸和丝氨酸代谢的理解。
