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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.

总结