从葡萄糖产生的酸盐与哺乳动物中的线粒体代谢的合
Xiaojing Liu1, Daniel E Cooper2, Ahmad A Cluntun1
1Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Duke University, Durham, NC 27710, USA.
Cell
|September 25, 2018
概括
酸盐在哺乳动物中量化产生酸盐,这是支持乙-CoA代谢的关键营养素. 这种新生酸的产生对细胞增殖至关重要,特别是在代谢压力或营养过剩期间.
科学领域:
- 生物化学
- 代谢途径
- 细胞代谢
背景情况:
- 乙酸是乙-CoA (Ac-CoA) 代谢的重要营养物质,影响脂质生成和蛋白质乙化.
- 然而,精确的内源性酸盐来源在很大程度上仍未确定.
- 了解酸盐的起源对于理解中央碳代谢及其在细胞功能中的作用至关重要.
研究的目的:
- 鉴定哺乳动物内源性乙酸的主要来源.
- 阐明从中心代谢物中产生酸盐的机制.
- 在细胞代谢和增殖中研究新酸盐生产的生理意义.
主要方法:
- 代谢流量分析以追踪从pyruvate产生的酸盐.
- 酶分析以描述新型的酸盐转化途径.
- 在代谢应激条件下的细胞实验 (例如线粒体功能障碍,ACLY缺乏) 以评估 de novo 酸盐的作用.
主要成果:
- 在哺乳动物中,酸盐是糖解的最终产物.
- 在营养过量和高活性葡萄糖代谢的情况下,酸盐的产量会增加.
- 两种不同的机制促进了酸盐转化:ROS合和新型酸脱酶活性.
- 酸的新生产维持了Ac-CoA池,并支持在代谢挑战的环境中细胞的增殖.
结论:
- 酸盐在哺乳动物中作为直接和显著的内源酸盐来源.
- 新发现的酸生产途径提供了对新陈代谢调节的见解.
- 在特定的代谢条件下,酸盐的产生在维持细胞功能和增殖方面起着至关重要的作用,对病理生理学有影响.
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