shotgun lipidomics identifies a paired rule for the presence of isomeric ether phospholipid molecular species猎枪lipidomics识别配对规则的存在异构醚磷脂分子的物种.pdfVIP

Shotgun Lipidomics Identifies a Paired Rule for the Presence of Isomeric Ether Phospholipid Molecular Species 1 1 1,2 1 Kui Yang , Zhongdan Zhao , Richard W. Gross , Xianlin Han * 1 Division of Bioorganic Chemistry and Molecular Pharmacology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America, 2 Department of Chemistry, Washington University, St. Louis, Missouri, United States of America Background. Ether phospholipids are abundant membrane constituents present in electrically active tissues (e.g., heart and the brain) that play important roles in cellular function. Alterations of ether phospholipid molecular species contents are associated with a number of genetic disorders and human diseases. Methodology/Principal Findings. Herein, the power of shotgun lipidomics, in combination with high mass accuracy/high resolution mass spectrometry, was explored to identify a paired rule for the presence of isomeric ether phospholipid molecular species in cellular lipidomes. The rule predicts that if an ether phospholipid A9-B is present in a lipidome, its isomeric counterpart B9-A is also present (where the 9 represents an ether linkage). The biochemical basis of this rule results from the fact that the enzymes which participate in either the sequential oxidation of aliphatic alcohols to fatty acids, or the reduction of long chain fatty acids to aliphatic alcohols (metabolic precursors of ether lipid synthesis), are not entirely selective with respect to acyl chain length or degree of unsaturation. Moreover, the enzymatic selectivity for the incorporation of different aliphatic chains into the obligatory precursor of ether lipids (i.e., 1-O-alkyl-glycero-3-phosphate) is also limited. Conclusions/Significance. This intrinsic am