酸盐脱酶激酶-1控制心肌细胞中的三糖醇水解
Michael G Atser1, Chelsea D Wenyonu1, Elyn M Rowe2
1Department of Cellular and Developmental Biology, Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
bioRxiv : the preprint server for biology
|October 28, 2024
概括
酸盐脱酶激酶 (PDK) 1通过影响脂肪分解,特别是营养缺乏期间,调节心脏细胞的燃料使用. 失去PDK1会影响脂肪代谢,但不会改变心肌细胞中葡萄糖的使用.
科学领域:
- 心脏病学 心脏病学
- 代谢调节 代谢调节 代谢调节
- 生物化学 生物化学
背景情况:
- 酸盐脱酶激酶 (PDK) 1在心肌细胞中丰富,对能量需求至关重要.
- PDK1在心肌细胞代谢中的特定作用尚不清楚.
- PDK活动影响碳水化合物和脂肪酸代谢.
研究的目的:
- 研究PDK1在调节心肌细胞燃料偏好的作用.
- 确定PDK1对心脏细胞脂质代谢的贡献.
主要方法:
- 在H9c2神经细胞中,lentiviral shRNA对PDK1进行了淘汰.
- 测量氧气消耗率和13C6葡萄糖的标签.
- 13C16 棕酸盐的追踪和脂质组分析.
- 在Pdk1淘汰赛小鼠中的验证.
主要成果:
- PDK1的敲除并没有影响PDH的整体活性,糖解或葡萄糖氧化.
- 在营养缺乏的情况下,PDK1的损失减少了三糖的循环和线粒体脂肪酸的利用.
- 在PDK1-抑制的细胞中,三糖醇的水解,而不是再化,受损.
- 对脂质新陈代谢的影响是特定于营养缺乏的条件.
结论:
- PDK1在调节心肌细胞脂质新陈代谢,特别是三糖醇周转方面发挥着新的作用.
- 这一功能独立于PDK1在葡萄糖代谢中的规范作用.
- 通过调节心脏细胞中的脂肪酸利用,PDK1对于适应营养缺乏至关重要.
更多相关视频
相关概念视频
cAMP-dependent Protein Kinase Pathways
6.1K
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,...
6.1K
Fats as Energy Storage Molecules
24.8K
Triglycerides are a form of long-term energy storage molecules. They are made of glycerol and three fatty acids. To obtain energy from fat, triglycerides must first be broken down by hydrolysis into their two principal components, fatty acids and glycerol. This process, called lipolysis, takes place in the cytoplasm. The resulting fatty acids are oxidized by β-oxidation into acetyl-CoA, which is used by the Krebs cycle. The glycerol that is released from triglycerides after lipolysis...
24.8K
What is Glycolysis?
163.9K
Overview
Cells make energy by breaking down macromolecules. Cellular respiration is the biochemical process that converts "food energy" (from the chemical bonds of macromolecules) into chemical energy in the form of adenosine triphosphate (ATP). The first step of this tightly regulated and intricate process is glycolysis. The word glycolysis originates from the Latin glyco (sugar) and lysis (breakdown). Glycolysis serves two main intracellular functions: generating ATP and generating...
Cells make energy by breaking down macromolecules. Cellular respiration is the biochemical process that converts "food energy" (from the chemical bonds of macromolecules) into chemical energy in the form of adenosine triphosphate (ATP). The first step of this tightly regulated and intricate process is glycolysis. The word glycolysis originates from the Latin glyco (sugar) and lysis (breakdown). Glycolysis serves two main intracellular functions: generating ATP and generating...
163.9K
Lipid Catabolism
1
Triglycerides serve as crucial long-term energy storage molecules in microorganisms, providing a dense source of metabolic energy. Their breakdown is mediated by lipases, which hydrolyze triglycerides into glycerol and free fatty acids. Each of these components follows distinct metabolic pathways, ultimately contributing to ATP synthesis and cellular energy homeostasis.Glycerol MetabolismGlycerol, released from triglyceride hydrolysis, is phosphorylated by glycerol kinase to form...
1
GPCRs Regulate Adenylyl Cylase Activity
5.3K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.3K
Transducer 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


