Phosphatidic acid biosynthesis: regulation of glycerol 3-phosphate acyltransferase

磷脂和三酰甘油（TAG）合成的调节在诸如肥胖症、糖尿病和动脉粥样硬化的疾病中起关键作用。甘油磷脂和TAG的合成始于甘油3-磷酸酰基转移酶（GPAT）对甘油3-磷酸的酰化，形成溶血磷脂酸（lysoPA），溶血磷脂酸立即转化为磷脂酸（PA）。GPAT被认为是调节一般脂质代谢的关键点。在20世纪50年代阐明了甘油脂质生物合成的途径，尽管在该领域取得了相当大的进展，但支配PA生物合成的调节的机制、控制限速GPAT步骤的特定分子机制和介导脂质代谢途径分配的精确决定因素尚不清楚。理解这种知识差距是细胞生物学的一个核心问题。使用酵母作为模型系统，我们打算进行GPAT的生物学，生物化学和分子表征，以了解这种代谢回路是如何调节和与其他回路整合的。

The regulation of phospholipid and triacylglycerol (TAG) synthesis plays a critical role in disorders such as obesity, diabetes and atherosclerosis. The synthesis of glycerophospholipids and TAG begins with the acylation of glycerol 3-phosphate by glycerol 3-phosphate acyltransferase (GPAT) to form lysophosphatidic acid (lysoPA) that is immediately converted to phosphatidic acid (PA). GPATs are thought to be key points of regulation of general lipid metabolism. The pathways of glycerolipid biosynthesis were elucidated in the 1950's and despite considerable advances in the field, the mechanisms governing the regulation of PA biosynthesis, the specific molecular mechanisms controlling the rate limiting GPAT step and the precise determinants mediating lipid metabolic pathway partitioning, are not known. Understanding this gap in knowledge is a central issue in cell biology. Using yeast as model system we intend to perform a biological, biochemical and molecular characterization of GPATs in order to understand how this metabolic circuit is regulated and integrated with other circuits.