Phosphatidic acid biosynthesis: regulation of glycerol 3-phosphate acyltransferase

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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.