定量流量分析揭示了依赖叶酸的NADPH生产
Jing Fan1, Jiangbin Ye2, Jurre J Kamphorst3
11] Department of Chemistry and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA [2].
Nature
|May 9, 2014
概括
叶酸代谢为细胞产生关键的减少功率,除了其在合成核酸中的作用外. 这一途径是细胞NADPH的重要来源,对于氧化还原平衡和细胞存活至关重要.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 代谢途径 代谢途径
背景情况:
- 腺三酸盐 (ATP) 是细胞工作的主要能量货币.
- 尼古丁胺胺氨基二核酸 (NADPH) 对于氧化还原防御和生物合成至关重要.
- 虽然ATP的产生途径已经得到了充分的研究,但NADPH的代谢需要进一步的研究.
研究的目的:
- 量化来自各种代谢途径的NADPH生产流.
- 研究叶酸代谢在细胞NADPH生成中的作用.
- 评估叶酸代谢对细胞氧化还原恒温的影响.
主要方法:
- 利用液体色谱-质谱测量来追踪用标记的基质进入NADPH.
- 采用碳标记和数学建模来测量代谢流.
- 进行了甲基基酸脱酶 (MTHFD) 的基因淘汰,以评估功能意义.
主要成果:
- 氧化酸酸盐路径是细胞增殖细胞中细胞质NADPH的最大贡献者.
- 血清驱动的单碳代谢对NADPH的产生有显著的贡献.
- 线粒体的一碳代谢也通过10-formyl-tetrahydrofolate氧化产生NADPH.
- MTHFD基因枯竭降低了细胞NADPH水平,增加了氧化应激敏感性.
结论:
- 叶酸代谢是细胞NADPH的关键,以前未知的来源.
- 叶酸代谢产生的NADPH对于维持还原氧平衡 (GSH/GSSG比率) 是必不可少的.
- 这一途径在细胞繁殖中起着双重作用:提供单碳单元和产生减少功率.
相关概念视频
01:29Role of Reduced Coenzymes NADH and FADH₂
The energy released from the breakdown of the chemical bonds within nutrients can be stored either through the reduction of electron carriers or in the bonds of adenosine triphosphate (ATP). In living systems, a small class of compounds functions as mobile electron carriers, molecules that bind to and shuttle high-energy electrons between compounds in pathways. The principal electron carriers that will be considered originate from the B vitamin group and are derivatives of nucleotides; they are...
01:28The Citric Acid Cycle: Output
The citric acid cycle is termed an amphibolic pathway as it operates both anabolically and catabolically. The cyclic reactions balance the flux of the substrates to provide an optimal concentration of NADH and ATP to the cell.
Regulation of Citric Acid Cycle
The citric acid cycle is regulated in several ways, including feedback inhibition, regulation of enzyme activities, and associated anaplerotic or cataplerotic pathways.
The primary substrate of the TCA cycle—acetyl CoA—is produced by the...
Regulation of Citric Acid Cycle
The citric acid cycle is regulated in several ways, including feedback inhibition, regulation of enzyme activities, and associated anaplerotic or cataplerotic pathways.
The primary substrate of the TCA cycle—acetyl CoA—is produced by the...
01:25Production of Organic Acids
Lactic acid, an important organic acid extensively applied in food, pharmaceutical, and biodegradable polymer industries, is primarily produced via microbial fermentation. This method is favored over chemical synthesis due to its environmental sustainability and capacity for enantiomerically pure product formation. Among various microbial processes, the fermentation of starch-based substrates stands out due to the abundance and renewability of raw materials like corn and potatoes.Hydrolysis of...