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 Tamir1,2,3,4, Shreya Chaudhary1,4, Annie X Li1,4
1Koch Institute for Integrative Cancer Research.
bioRxiv : the preprint server for biology
|September 11, 2024
概括
细胞信号通过酸化调节新陈代谢. 这项研究确定了影响肥胖症肝脏新陈代谢的关键铁位,揭示了它们如何控制酶活性和氧化还原平衡,具有治疗干预的潜力.
科学领域:
- 生物化学和分子生物学
- 代谢调节 代谢调节 代谢调节
- 细胞信号传输 细胞信号传输
背景情况:
- 代谢平衡依赖于由细胞信号网络协调的适应性代谢.
- 翻译后的修改,特别是酸化,动态调节代谢酶.
- 许多已识别的酸化部位对酶活性和系统代谢的功能影响尚不清楚.
研究的目的:
- 根据它们在功能域内的位置,对代谢酶的酸化位进行分层.
- 为了确定肥胖症改变的酸盐,并研究酸铁 (pY) 对肝脏新陈代谢的功能影响.
- 描述参与氧化还原和还原代谢的关键代谢酶上的特定预测性pY位点.
主要方法:
- 生物信息学分析相对于酶域的酸盐位置.
- 在高脂肪饮食 (HFD) 诱导的肥胖模型中,进行多个omics分析 (光蛋白质和代谢学).
- 进行CRISPR干扰救援实验和稳定同位素追踪,以功能性地描述pY站点.
主要成果:
- 酸盐,特别是酸铁 (pY),在氧化还原酶的功能和二元化域附近被丰富.
- HFD诱导了氧化和还原性新陈代谢在蛋白质组和代谢组水平的性别特异性失调.
- 发现GSTP1和UMPS上的特定pY位点抑制了酶活性,而IDH1上的pY位点增强了活性,促进了还原性炭化.
结论:
- 酸化,特别是pY,在微调肝脏新陈代谢和氧化还原平衡中起着至关重要的作用.
- 肥胖引起的代谢失调涉及特定的酸盐变化,可以通过抗氧化剂调节.
- 这项研究提供了关于细胞信号如何与代谢途径融合以维持恒常的机制的见解.
相关概念视频
02:54Protein Kinases and Phosphatases
13.1K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.1K
01:02Phosphorylation
50.1K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
50.1K
01:27Transducer Mechanism: Enzyme-Linked Receptors
2.4K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.4K
01:25cAMP-dependent Protein Kinase Pathways
6.2K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.2K
01:19Regulation of Metabolism
9.3K
Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...
9.3K