对代谢酶酸化的结构和系统表征确定了肥胖症中性别特异的代谢重编程
Tigist Y Tamir1, Shreya Chaudhary2, Annie X Li2
1Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Molecular cell
|May 29, 2025
概括
通过酶酸化,细胞信号微调新陈代谢. 这项研究确定了特定的酸盐及其在代谢调节中的作用,为肥胖和抗氧化作用提供了洞察力.
科学领域:
- 细胞的新陈代谢
- 生物化学 生物化学
- 系统生物学 系统生物学
背景情况:
- 适应性新陈代谢对于细胞能量和平衡至关重要.
- 酶酸化是代谢网络的关键调节机制.
- 代谢酶上的酸盐通常位于功能或二元化领域附近.
研究的目的:
- 为了结构性地分析酸对代谢酶的作用.
- 研究高脂肪饮食 (HFD) 诱导的代谢失调和性别特异性影响.
- 探索酸铁 (pY) 在代谢控制中的作用及其与抗氧化剂的可逆性.
主要方法:
- 对酸盐在代谢酶上的结构分析.
- 在高脂肪饮食 (HFD) 诱导的肥胖小鼠模型中进行多组学分析.
- 计算建模用于预测酸盐-代谢物协会.
- 克里斯普尔干扰 (CRISPRi) 救援和稳定同位素追踪,以描述特定酸盐的功能作用.
主要成果:
- 大多数酸盐都在氧化还原酶上,在活性位点或二聚体接口附近.
- 酸铁 (pY) 在功能领域中占有过多的比例,尽管其固体质量较低.
- HFD诱导了pY和代谢物的性别特异性失调,可通过丁酸酸盐 (BHA) 逆转.
- 识别和描述了GSTP1,IDH1和UMPS上的预测pY站点的功能角色.
结论:
- 细胞信号传递,特别是酸化,动态调节酶活性和新陈代谢.
- pY位点在代谢适应和失调中起着重要的作用.
- 抗氧化剂治疗可以逆转饮食引起的代谢干扰.
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