Novel aspects of phosphatidylcholine metabolism

磷脂酰胆碱代谢的新方面

基本信息

批准号：
9303689
负责人：
JANA L VOGT
金额：
$ 41.39万
依托单位：
DUQUESNE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-12-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9303689
关键词：
Acyl Coenzyme A Acylation Acyltransferase Affect Anabolism Biochemical Candida albicans Cell physiology Cells Cytidine Diphosphate Choline Defect Development Diabetes Mellitus Disease Enzymes Eukaryotic Cell Event Excision Gene Expression Genes Genetic Glycerol Glycerophospholipids Growth Homeostasis Label Lecithin Link Lipids Lysophosphatidylcholines Lysophospholipids Malignant Neoplasms Mass Spectrum Analysis Mediating Medical Membrane Membrane Lipids Metabolic Metabolism Methylation Modernization Molecular Molecular Genetics Monitor Mutation Obesity Organism Pathogenicity Pathway interactions Phenotype Phosphatidylcholine Biosynthesis Phospholipase Phospholipids Positioning Attribute Property Protein Family Proteins Radiolabeled Regulation Research Role Saccharomyces cerevisiae Sphingolipids Techniques Testing Thick Transacylase Ursidae Family Vertebral column Vertebrates Virulence attenuation base deacylation enzyme activity experimental study fluidity fungus graduate student in vivo inhibitor/antagonist member novel overexpression response undergraduate student

项目摘要

Summary Membrane homeostasis is a fundamental aspect of cell function and requires the coordinated control of multiple metabolic activities, including biosynthetic enzymes involved in lipid synthesis, phospholipases involved in lipid turnover and acyltransferases involved in lipid remodeling. Defects in lipid homeostasis can contribute to the development of many diseases, including obesity, diabetes, and cancer. Phosphatidylcholine (PC) is the major glycerophospholipid found in most eukaryotic cells. Alterations in its synthesis, turnover and remodeling are associated with cellular malfunctions and disease states. PC, like other phospholipids, consists of multiple molecular species based on acyl chain differences. Acyl chain content affects fundamental membrane properties such as thickness, curvature, and fluidity. Differences in PC species can be generated during biosynthesis or as a result of remodeling, which typically involves deacylation to a lysophospholipid followed by reacylation. The complete deacylation of PC produces glycerophosphocholine (GPC). We have identified a novel enzyme that expands our understanding of PC biosynthesis and remodeling, a GPC acyltransferase termed Gpc1. Our central hypothesis is that Gpc1 contributes to PC metabolism in vivo, and that the remodeling of PC species through deacylation and reacylation is regulated in coordination with sphingolipid and PC biosynthetic pathways to maintain lipid homeostasis. We propose to examine the cellular role of Gpc1 in PC metabolism, its regulation with regard to PC and sphingolipid biosynthesis, and phenotypes associated with alterations in its expression.

概括膜稳态是细胞功能的基本方面，需要协调控制多种代谢活性，包括参与脂质合成的生物合成酶，磷脂酶参与脂质周转和参与脂质重塑的酰基转移酶。脂质稳态缺陷可以有助于许多疾病的发展，包括肥胖，糖尿病和癌症。磷脂酰胆碱（PC）是在大多数真核细胞中发现的主要甘油磷脂。改变它的合成，周转和重塑与细胞故障和疾病状态有关。个人电脑，与其他磷脂一样，基于酰基链差异，由多种分子物种组成。酰基链含量会影响厚度，曲率和流动性等基本膜特性。 PC物种的差异可以在生物合成期间产生，也可以是由于重塑而产生的。通常涉及脱氧于溶血磷脂，然后重新酰化。完整的脱酰化 PC产生甘油磷胆碱（GPC）。我们已经确定了一种扩展我们的新型酶了解PC生物合成和重塑，这是一种称为GPC1的GPC酰基转移酶。我们的中心假设是GPC1在体内有助于PC代谢，并且PC物种的重塑通过脱酰化和重聚，通过与鞘脂和PC生物合成的协调调节保持脂质稳态的途径。我们建议检查GPC1在PC中的细胞作用代谢，对PC和鞘脂生物合成的调节以及相关的表型随着其表达的改变。