哺乳动物将内源性毒性甲转化为单碳代谢
Guillermo Burgos-Barragan1, Niek Wit1, Johannes Meiser2
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Nature
|August 17, 2017
概括
补充叶酸衍生物会产生甲, 排毒这种甲为细胞生长提供了必不可少的单碳单元,
科学领域:
- 细胞代谢
- 分子生物学
- 遗传学
背景情况:
- 由叶酸驱动的单碳 (1C) 循环对于合成核酸,氨基酸和表观遗传修饰至关重要.
- 这种新陈代谢途径可能无意中产生甲,一种能够将蛋白质和DNA交叉连接的基因毒剂.
研究的目的:
- 研究叶酸循环中产生的甲对细胞活力的作用.
- 探索甲解毒与核酸合成之间的联系.
- 为细胞代谢确定1C单位的替代来源.
主要方法:
- 补充细胞 (人,小鼠,) 与四叶酸和其他容易氧化的叶酸衍生物.
- 与甲排毒和DNA交叉连接修复途径相关的细胞活力的评估.
- 从叶酸分解生成甲的分析.
- 在甲排毒过程中追踪甲酸盐的产生及其对核酸合成的影响.
主要成果:
- 用特定的叶酸衍生物补充导致人类,小鼠和细胞缺乏甲排毒或DNA交叉连接修复.
- 甲通过叶酸骨干的氧化分解产生.
- 人体细胞中的甲排毒产生甲酸盐,它支持核酸合成.
- 这种甲酸来源的1C供应可以维持无法利用血清素的细胞的生长.
结论:
- 叶酸循环是一种内源的甲.
- 这种甲的排毒产生甲酸盐, 一个重要的1C单元, 支持细胞代谢, 特别是核酸合成.
- 这种途径在特定的细胞环境中提供1C单位供应的补偿机制.
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