一类的基因素脱乙酶催化了氨酸的乳酸化
Takeshi Tsusaka1, Mohd Altaf Najar2, Isha Sharma1
1Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.
bioRxiv : the preprint server for biology
|March 10, 2025
概括
基因组脱乙酶 (HDACs) 1,2,3催化氨酸乳酸化 (Kla),是一种代谢修饰. 这一发现揭示了HDACs是负责细胞中Kla形成的大多数关键酶.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 代谢学 代谢学 代谢学
背景情况:
- 代谢和翻译后修改 (PTMs) 越来越多地被认为是相互关联的过程.
- 乳酸盐是无氧糖解的产物,可以通过氨酸乳化 (Kla) 共同修饰蛋白质.
- 现有的Kla形成模型涉及乳基CoA,非酶反应或其他酶.
研究的目的:
- 调查I类组胺脱乙酶 (HDACs) 在催化氨酸乳酸化 (Kla) 中的作用.
- 确定HDAC是否可以逆转其正规脱乙烯化反应以促进乳酸化.
- 阐明细胞环境中Kla形成的主要机制.
主要方法:
- 生物化学测试以评估酶活性.
- 药理上抑制HDACs的作用.
- 基因操纵来改变HDAC的表达.
- 透析实验用于研究反应的可逆性和依赖乳酸度.
- 细胞内乳糖-CoA水平的量化.
主要成果:
- 发现I类HDACs (1,2,3) 能够催化氨酸乳酸化 (Kla).
- 由HDAC催化的Kla形成占了细胞内Kla的大部分.
- 反应是可逆的,并且取决于乳酸度.
- 克拉的丰富度与细胞内乳糖-CoA水平没有直接相关.
结论:
- 第I类HDACs (1,2,3) 是负责催化氨酸乳酸化 (Kla) 的主要酶.
- HDACs可以逆转其正规功能,将乳酸盐添加到氨酸残留物中.
- 提出了一个新的模型,其中HDACs通过酶添加乳酸,独立于大部分Kla形成的乳酸-CoA水平.
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