确定一种替代的甘油三生物合成途径
Gian-Luca McLelland1, Marta Lopez-Osias2, Cristy R C Verzijl3
1Oncode Institute, Division of Biochemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands. g.mclelland@nki.nl.
Nature
|August 30, 2023
概括
研究人员在人类中发现了一种合成三糖醇 (TAG) 的新途径,其中涉及DIESL和TMX1蛋白,这对能量稳定和线粒体功能至关重要.
科学领域:
- 生物化学
- 细胞生物学
- 代谢调节
背景情况:
- 三糖醇 (TAG) 是重要的能量储存物, 但它们的失调与肥胖和心脏病有关.
- 已知用于TAG合成的人类酶是二甲基糖醇O-乙转移酶 (DGAT1和DGAT2).
- 在人体中存在其他TAG合成途径尚未被探索.
研究的目的:
- 研究人类细胞中三糖醇 (TAG) 合成的潜在替代途径.
- 确定涉及DGAT1和DGAT2以外的TAG生物合成的新酶和调节剂.
主要方法:
- 在人类单体细胞中破坏已知的二甲基糖醇O-转移酶 (DGAT) 途径.
- 使用代遗传学来选其他TAG合成系统.
- 使用生物化学和细胞测试来描述已识别的蛋白质 (DIESL和TMX1) 的功能.
- 在大肠杆菌中表达人类DIESL以确认其TAG合成能力.
- 在小鼠模型中研究DIESL的生理作用.
主要成果:
- 确定了一种替代的TAG合成途径,涉及转移酶DIESL (TMEM68) 和其调节器TMX1.
- TMX1 调节了内等离子网中的 DIESL 活性;其缺失导致了不受控制的脂质滴形成.
- DIESL作为一种自主TAG合成酶,甚至能够在细菌中合成TAG.
- 通过利用膜脂,DIESL可以合成TAG,并在营养缺乏时支持线粒体功能.
- 在小鼠中,DIESL缺乏会影响产后生长和能量平衡.
结论:
- 在人类中发现了一种新的DGAT独立的TAG生物合成途径,该途径由DIESL调节,并由TMX1调节.
- 这种由DIESL驱动的途径在细胞能量代谢中起着至关重要的作用,特别是在脂质饥饿的条件下.
- 这些发现显示DIESL是维护线粒体功能和整体能量平衡的关键因素,对代谢疾病有影响.
相关概念视频
Biosynthesis of Lipids
35
Microbial membranes exhibit remarkable diversity in lipid composition, reflecting evolutionary adaptations to various environmental conditions. The three domains of life—Bacteria, Archaea, and Eukarya—synthesize membrane lipids through distinct biosynthetic pathways, leading to fundamental structural differences that impact membrane stability, function, and adaptability.Fatty Acid-Based Lipids in Bacteria and EukaryaBacteria and eukaryotes share a common fatty acid biosynthesis...
35
Fats as Energy Storage Molecules
25.2K
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...
25.2K
Lipid Catabolism
48
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...
48
Overview of Lipid Metabolism
1.7K
Lipid metabolism is a crucial process in the human body that involves the synthesis and degradation of lipids. This process is essential for energy production, cell membrane formation, and hormone production, among other functions.
Lipolysis: The Breakdown of Lipids:
Lipolysis is the process of breaking down lipids, particularly triglycerides, into glycerol and fatty acids. This process typically occurs in the adipose tissue and is triggered by various hormones, including glucagon and...
Lipolysis: The Breakdown of Lipids:
Lipolysis is the process of breaking down lipids, particularly triglycerides, into glycerol and fatty acids. This process typically occurs in the adipose tissue and is triggered by various hormones, including glucagon and...
1.7K
Other Glycolytic Pathways
44
The pentose phosphate pathway (PPP) operates in parallel with glycolysis, facilitating the metabolism of both pentoses and glucose. This pathway consists of two distinct phases: the oxidative and non-oxidative phases. While it does not directly generate ATP, the intermediates formed during the process can integrate into glycolysis, contributing to cellular energy metabolism when required.Oxidative Phase: NADPH ProductionThe oxidative phase of the pentose phosphate pathway is primarily...
44
Overview of Fatty Acid Metabolism
30.8K
Lipids also are sources of energy that power cellular processes. Like carbohydrates, lipids are composed of carbon, hydrogen, and oxygen, but these atoms are arranged differently. Most lipids are nonpolar and hydrophobic. Major types include fats and oils, waxes, phospholipids, and steroids.
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
30.8K


