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中华临床医师杂志(电子版) ›› 2026, Vol. 20 ›› Issue (02) : 145 -150. doi: 10.3877/cma.j.issn.1674-0785.2026.02.009

综述

一碳代谢在认知障碍中的作用机制及研究进展
代聪聪1, 邬宏伟1, 高一3, 周琪2, 户占飞2, 李海波2, 宋健楠1,2,()   
  1. 1 010000 呼和浩特,内蒙古医科大学
    2 024000 赤峰,赤峰市医院麻醉科
    3 100080 北京,北京世纪坛医院麻醉科
  • 收稿日期:2025-12-10 出版日期:2026-02-28
  • 通信作者: 宋健楠
  • 基金资助:
    赤峰市自然科学研究项目(SZR24087)

Advances in understanding the role of one-carbon metabolism in cognitive impairment

Congcong Dai1, Hongwei Wu1, Yi Gao3, Qi Zhou2, Zhanfei Hu2, Haibo Li2, Jiannan Song1,2,()   

  1. 1 Inner Mongolia Medical University, Hohhot 010000, China
    2 Department of Anesthesiology, Chifeng Municipal Hospital, Chifeng 024000, China
    3 Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100080, China
  • Received:2025-12-10 Published:2026-02-28
  • Corresponding author: Jiannan Song
引用本文:

代聪聪, 邬宏伟, 高一, 周琪, 户占飞, 李海波, 宋健楠. 一碳代谢在认知障碍中的作用机制及研究进展[J/OL]. 中华临床医师杂志(电子版), 2026, 20(02): 145-150.

Congcong Dai, Hongwei Wu, Yi Gao, Qi Zhou, Zhanfei Hu, Haibo Li, Jiannan Song. Advances in understanding the role of one-carbon metabolism in cognitive impairment[J/OL]. Chinese Journal of Clinicians(Electronic Edition), 2026, 20(02): 145-150.

一碳代谢作为细胞内一种重要的甲基供体转运通路,参与DNA甲基化、组蛋白修饰和神经递质合成等众多生理过程,在脑功能维护和损伤发生方面均起着至关重要的作用。研究表明,一碳代谢异常可通过干扰表观遗传修饰、神经元能量代谢、神经递质合成等病理生理过程,直接或间接参与与阿尔茨海默病、血管性认知障碍等认知障碍的发生与发展,因而得到临床广泛关注。因此,为了系统中总结相关方面的研究成果,本文就一碳代谢与神经发育和认知的相关关系、相关的代谢通路及代谢物水平的干预等内容进行了相关研究进展的阐述,为临床上一碳代谢相关性疾病的诊治提供参考。

One-carbon metabolism is a fundamental intracellular pathway responsible for methyl donor transfer, governing essential processes such as epigenetic regulation and neurotransmitter synthesis, and thus plays a pivotal role in brain health and disease. Dysregulation of this metabolic pathway is increasingly linked to cognitive disorders like Alzheimer's disease and vascular cognitive impairment, where it contributes to pathology by disrupting epigenetic programming, neuroenergetics, and synaptic transmission. This review synthesizes current evidence to elucidate the mechanistic connections between one-carbon metabolism and cognitive function, focusing on its metabolic pathways, key pathogenic mediators, such as homocysteine, and potential therapeutic interventions targeting these pathways.

图1 一碳代谢通路示意图。图a为一碳代谢循环,图b为细胞中一碳代谢全通路图。Folate为叶酸;DHF为二氢叶酸;THF为四氢叶酸;5,10-me-THF为5,10-亚甲基四氢叶酸;10-formyl-THF为10-甲酰基四氢叶酸;5-me-THF为5-甲基四氢叶酸;Methionine为甲硫氨酸;Hcy为同型半胱氨酸NADP+/NADPH9为烟酰胺腺嘌呤二核苷酸磷酸;B6为维生素B6;Glycine为甘氨酸;Sarcosine为肌氨酸;Cysteine为半胱氨酸;Cystathionine为胱硫醚;Homoserine为高丝氨酸;dTMP为脱氧胸苷酸;SAM为S-腺苷甲硫氨酸;SAH为S-腺苷同型半胱氨酸;Adenosine为腺苷;Formate为甲酸盐;GSH为谷胱甘肽
表1 参与一碳代谢的酶及其功能
英文缩写 中文全称 作用
DHFR 二氢叶酸还原酶 将DHF还原为THF,维持叶酸循环
SHMT2 丝氨酸羟甲基转移酶2 在线粒体中催化丝氨酸和THF转化为甘氨酸和5,10-亚甲基-THF,提供一碳单位
SHMT 丝氨酸羟甲基转移酶 在胞质中催化丝氨酸和THF转化为甘氨酸和5,10-亚甲基-THF,提供一碳单位
MTHFD1 亚甲基四氢叶酸脱氢酶1 催化5,10-亚甲基-THF进一步转化为10-甲酰基-THF
MTHFD1L 亚甲基四氢叶酸脱氢酶1L 在线粒体中催化10-甲酰基-THF的合成,参与一碳单位储存和利用
MTHFD2/2L 亚甲基四氢叶酸脱氢酶2 在线粒体中催化5,10-亚甲基-THF转化为5,10-亚甲酰基-THF
MTHFR 亚甲基四氢叶酸还原酶 生成5-甲基四氢叶酸,为同型半胱氨酸再甲基化提供甲基
MTR 甲硫氨酸合酶 催化同型半胱氨酸再甲基化生成甲硫氨酸
MAT Ⅰ/Ⅲ 甲硫氨酸腺苷转移酶 Ⅰ/Ⅲ 将甲硫氨酸活化为甲基供体SAM
DNMT DNA甲基转移酶 利用SAM进行DNA甲基化
AHCY S-腺苷同型半胱氨酸水解酶 水解SAH生成同型半胱氨酸和腺苷,维持甲基化循环
TYMS 胸苷酸合酶 催化dUMP转化为dTMP,使用5,10-亚甲基-THF作为甲基供体,合成DNA
ALDH1L1 醛脱氢酶1家族成员L1 催化10-甲酰基-THF转化为NADPH和CO2,调节一碳单位
GNMT 甘氨酸N-甲基转移酶 催化甘氨酸和SAM转化为肌氨酸和SAH,调节甲基化反应
CBS 胱硫醚β-合酶 催化同型半胱氨酸和丝氨酸转化为胱硫醚,启动转硫途径
CTH 胱硫醚-γ-裂解酶 负责分解胱硫醚以生成半胱氨酸
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