一类的基因素脱乙酶催化了氨酸的乳酸化
Michelangelo B Gonzatti1, Jordi C J Hintzen2, Isha Sharma1
1Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.
The Journal of biological chemistry
|August 20, 2025
概括
基因组脱乙酶 (HDACs) 可以催化氨酸乳酸化 (Kla),这是一种代谢修饰. 这项研究揭示了HDAC是Kla形成的主要驱动因素,独立于乳基-CoA水平.
科学领域:
- 生物化学 生物化学
- 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) 越来越被认为是相互关联的.
- 乳酸盐是无氧代谢的产物,可以通过氨酸乳化 (Kla) 共同修饰蛋白质.
- 现有的Kla形成机制包括涉及乳糖CoA或乳糖氨酸的酶和非酶途径.
研究的目的:
- 调查I类组胺脱乙酶 (HDACs) 在催化氨酸乳酸化 (Kla) 中的潜在作用.
- 为了确定HDAC是否对细胞内Kla形成有显著的贡献.
- 为了阐明乳糖CoA水平和Kla丰度之间的关系.
主要方法:
- 生物化学试验,以评估乳化中的HDAC活性.
- 药理上抑制HDACs以观察对Kla的影响.
- 基因方法来操纵HDAC表达和研究Kla.
- 直接量化细胞内乳酸-CoA.直接量化.
- 透析实验以评估反应的可逆性.
主要成果:
- 发现HDACs (1,2,3) 足以催化Kla的形成.
- 鉴定出HDACs是氨酸乳酸化的主要驱动因素.
- 克拉的形成被证明是依赖乳酸度的可逆反应.
- 细胞内Kla丰度可能与乳酸-CoA水平脱.
结论:
- 第I类HDAC (1,2,3) 具有乳酸转移酶活性.
- HDACs在酵素形成的lysine乳酸化中起着至关重要的作用.
- 提出了一个模型,其中HDACs是乳酸盐添加到lysine残留的主要媒介,独立于乳酸-CoA度.
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