Novel aspects of phosphatidylcholine metabolism

磷脂酰胆碱代谢的新方面

• 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
• 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

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 膜稳态是细胞功能的一个基本方面，需要协调控制细胞膜的稳态。 多种代谢活动，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 会导致许多疾病，包括肥胖症、糖尿病和癌症。 磷脂酰胆碱（PC）是大多数真核细胞中发现的主要甘油磷脂。的改变 其合成、周转和重塑与细胞功能障碍和疾病状态相关。PC， 与其它磷脂一样，由基于酰基链差异的多种分子种类组成。酰基 链含量影响膜的基本性质，例如厚度、曲率和流动性。 PC种类的差异可以在生物合成过程中产生，也可以是重塑的结果， 典型地包括脱酰化成溶血磷脂，然后再酰化。的完全脱酰化 PC产生甘油磷酸胆碱（GPC）。我们发现了一种新的酶， 为了了解PC生物合成和重塑，GPC酰基转移酶称为Gpc1。我们的中央 一种假说认为，Gpc 1参与体内PC代谢， 通过去酰化和再酰化与鞘脂和PC生物合成协调调节 维持脂质稳态的途径。我们建议研究Gpc1在PC中的细胞作用， 代谢，其在PC和鞘脂生物合成方面的调节，以及相关的表型 其表达方式发生了变化。