statistical analysis of the processes controlling choline and ethanolamine glycerophospholipid molecular species composition统计分析的过程控制胆碱和乙醇胺glycerophospholipid分子物种组成.pdf

Statistical Analysis of the Processes Controlling Choline and Ethanolamine Glycerophospholipid Molecular Species Composition 1. 1. 2 2 3 2 Kourosh Zarringhalam , Lu Zhang , Michael A. Kiebish , Kui Yang , Xianlin Han , Richard W. Gross , Jeffrey Chuang1* 1 Department of Biology, Boston College, Chestnut Hill, Massachusetts, United States of America, 2 Division of Bioorganic Chemistry and Molecular Pharmacology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America, 3 Sanford Burnham Medical Research Institute, Diabetes and Obesity Research Center, Orlando, Florida, United States of America Abstract The regulation and maintenance of the cellular lipidome through biosynthetic, remodeling, and catabolic mechanisms are critical for biological homeostasis during development, health and disease. These complex mechanisms control the architectures of lipid molecular species, which have diverse yet highly regulated fatty acid chains at both the sn1 and sn2 positions. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) serve as the predominant biophysical scaffolds in membranes, acting as reservoirs for potent lipid signals and regulating numerous enzymatic processes. Here we report the first rigorous computational dissection of the mechanisms influencing PC and PE molecular architectures from high- throughput shotgun lipidomic data. Using novel statistical approaches, we have analyzed multidimensional mass spectrometry-based shotgun lipidomic data from developmental mouse heart and mature mouse heart, lung, brain, and liver tissues. We show that in