title: What makes the bioactive lipids phosphatidic acid and lysophosphatidic acid so special?
abstract: Phosphatidic acid and lysophosphatidic acid are minor but important anionic bioactive lipids involved in a number of key cellular processes, yet these molecules have a simple phosphate headgroup. To find out what is so special about these lipids, we determined the ionization behavior of phosphatidic acid (PA) and lysophosphatidic acid (LPA) in extended (flat) mixed lipid bilayers using magic angle spinning 31P NMR. Our data show two surprising results. First, despite identical phosphomonoester headgroups, LPA carries more negative charge than PA when present in a phosphatidylcholine bilayer. Dehydroxy-LPA [1-oleoyl-3-(phosphoryl)propanediol] behaves in a manner identical to that of PA, indicating that the difference in negative charge between LPA and PA is caused by the hydroxyl on the glycerol backbone of LPA and its interaction with the phosphomonoester headgroup. Second, deprotonation of phosphatidic acid and lysophosphatidic acid was found to be strongly stimulated by the inclusion of phosphatidylethanolamine in the bilayer, indicating that lipid headgroup charge depends on local lipid composition and will vary between the different subcellular locations of (L)PA. Our findings can be understood in terms of a hydrogen bond formed within the phosphomonoester headgroup of (L)PA and its destabilization by competing intra- or intermolecular hydrogen bonds. We propose that this hydrogen bonding property of (L)PA is involved in the various cellular functions of these lipids.
authors.affiliation: Department of Biochemistry of Membranes, Bijvoet Center, Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands. e.e.kooijman@chem.uu.nl
authors.forename: Edgar E
authors.initials: EE
authors.lastname: Kooijman
authors.forename: Karen M
authors.initials: KM
authors.lastname: Carter
authors.forename: Emma G
authors.initials: EG
authors.lastname: van Laar
authors.forename: Vladimir
authors.initials: V
authors.lastname: Chupin
authors.forename: Koert N J
authors.initials: KN
authors.lastname: Burger
authors.forename: Ben
authors.initials: B
authors.lastname: de Kruijff
mesh_terms: D002462:Cell Membrane / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000737:chemistry; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000737:chemistry; D007477:Ions / Q000737:chemistry; D016018:Least-Squares Analysis; D008051:Lipid Bilayers / Q000737:chemistry*; D008246:Lysophospholipids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008567:Membranes, Artificial; D008958:Models, Molecular; D015394:Molecular Structure; D010712:Phosphatidic Acids / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011522:Protons; D017186:Titrimetry
chemical_list: D007477:Ions; D008051:Lipid Bilayers; D008246:Lysophospholipids; D008567:Membranes, Artificial; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011522:Protons; C037657:dioleoylphosphatidic acid; C094877:dioleoyl phosphatidylethanolamine; C017251:1,2-oleoylphosphatidylcholine; C032881:lysophosphatidic acid