鉴定UGT8作为哺乳动物中的单甲酸二甲糖醇合成酶的特征
Yohsuke Ohba1,2, Mizuki Motohashi1, Makoto Arita1,2,3,4
1Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
Journal of biochemistry
|December 10, 2024
概括
哺乳动物细胞通过UGT8酶合成单甲二甲糖醇 (MGDG). 这种酶对膜脂质和和内质网膜功能至关重要,影响细胞应激反应.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 利皮多米克 (Lipidomics) 是一种消化剂.
背景情况:
- 单甲酸甲糖醇 (MGDG) 是一种关键的植物膜脂质,但其在哺乳动物中的作用和合成知之甚少.
- 以前的研究表明,UGT8是一种胺银河系转移酶,可能参与哺乳动物MGDG生物合成.
研究的目的:
- 为了识别哺乳动物MGDG合成酶.
- 阐明MGDG及其合成酶在哺乳动物细胞中的功能.
主要方法:
- 使用液体染色学四极飞行时间质谱法 (LC-QTOF-MS) 来量化MGDG的脂管学.
- 通过CRISPR/Cas9基因编辑,创建UGT8淘汰赛 (KO) 的HeLa细胞.
- 在体外酶活性测定和局部定向突变发生.
- 细胞局部化研究和对未折叠蛋白质反应的分析.
主要成果:
- 在HeLa细胞中成功量化了内源MGDG水平.
- 在UGT8KO细胞中,MGDG被完全耗尽,在UGT8过度表达时,其产量增加.
- UGT8在体外表现出MGDG生物合成活性,His358对其功能至关重要.
- UGT8定位在内质网膜中,其缺乏会损害与膜脂和相关的未折叠蛋白质反应.
结论:
- 在哺乳动物中,UGT8被确定为主要的MGDG合成酶.
- UGT8在调节膜脂和和细胞应激信号通路方面发挥着重要作用.
关键词:
细胞内膜网膜的压力应激葡萄糖类脂类化合物 葡萄糖类脂类化合物质谱测量质谱测量质谱测量质谱测量质量测量质谱测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量膜脂质 膜脂质是一种不折叠的蛋白质反应反应更多相关视频
12:29Generation of Null Mutants to Elucidate the Role of Bacterial Glycosyltransferases in Bacterial Motility
Published on: March 11, 2022
2.2K
10:12A Fluorescence-based Assay for Characterization and Quantification of Lipid Droplet Formation in Human Intestinal Organoids
Published on: October 13, 2019
9.0K
相关概念视频
Oligosaccharide Assembly
2.8K
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
2.8K
Protein Folding Quality Check in the RER
3.7K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
3.7K
Glucose Transporters
22.5K
Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
22.5K
Protein Glycosylation
6.8K
Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
Glycosylation occurs in...
6.8K
Proteoglycans
3.9K
Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
3.9K
Biosynthesis of Polysaccharides
Polysaccharides such as glycogen and starch are synthesized from nucleoside diphosphate sugars, primarily uridine diphosphate glucose (UDPG) and adenosine diphosphate glucose (ADPG). These activated glucose donors act as key intermediates in carbohydrate metabolism and biosynthesis. UDPG primarily involves glycogen synthesis in animals and many bacteria, while ADPG plays a fundamental role in starch synthesis in plants and certain bacteria.UDPG is formed when glucose-1-phosphate reacts with...
