<br>丝氨酸和丝氨酸代谢在健康和疾病中的信号传导属性的全面综述,International Journal of Biological Macromolecules

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丝氨酸和丝氨酸代谢在健康和疾病中的信号传导属性的全面综述
International Journal of Biological Macromolecules ( IF 7.7 ) Pub Date : 2024-01-20 , DOI: 10.1016/j.ijbiomac.2024.129607
Di Wu ₁ , Kejia Zhang ₁ , Faheem Ahmed Khan ₂ , Nuruliarizki Shinta Pandupuspitasari ₃ , Kaifeng Guan ₄ , Fei Sun ₁ , Chunjie Huang ₁

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丝氨酸是一种具有不断扩展的代谢和非代谢信号传导属性的代谢物。通过为大分子生物合成和功能修饰提供单碳单位，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，以创造有利于生存和侵袭性的代谢状态，这使得干预与癌症相关的丝氨酸代谢重排成为一种有前景的癌症治疗策略。除了为先天免疫调节中的甲基化提供甲基供体外，丝氨酸代谢还为线粒体 tRNA 甲酰化生成甲酰基供体，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，并且严重依赖星形胶质细胞的丝氨酸来产生丝氨酸来塑造突触可塑性。在这里，我们概述了最近的发现，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疾病中的医学意义。还讨论了丝氨酸代谢的代谢控制以及表观遗传和翻译后调节。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宝贵的线索，这将有助于更深入地了解细胞生理学和病理学中的丝氨酸和丝氨酸代谢。

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A comprehensive review on signaling attributes of serine and serine metabolism in health and disease

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 -serine for production of -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.

更新日期：2024-01-20

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