Hydrogen bonding increases the charge of phosphatidic acid (PA) and lysophosphatidic acid (LPA). (a) The phosphomonoester headgroup of LPA forms an intramolecular hydrogen bond. In the protonated phosphomonoester of LPA (left) a proton is shared between two hydroxyl oxygens (purple dashed lines). Hydrogen bonding (green dashed lines) between the sn2 hydroxyl and the phosphomonoester of LPA competes with the shared proton for oxygen electrons, which facilitates dissociation of the proton lowering the pK
. (b) Hydrogen bonding between the phosphomonoester of PA and the primary amine of the headgroup of PE, or lysines and arginines of proteins, results in deprotonation of the phosphomonoester, lowering its pK
and increasing its negative charge. The abundance of PE in cellular membranes is likely a significant factor regulating the pK
of both PA and LPA . Hydrogen bonding between proteins and PA is described by the electrostatic/hydrogen bond switch mechanism .