Permeation of aromatic carboxylic acids across lipid bilayers: the pH-partition hypothesis revisited.
According to the pH-partition hypothesis the charged species of organic compounds do not contribute to lipid bilayer permeation as they generally show negligible partitioning into n-octanol. With this assumption, membrane permeation is related to the molar fraction of the neutral species at a particular pH. A recently developed permeation assay permits us to directly determine pH-dependent permeation of aromatic carboxylic acids. Tb(3+)-loaded liposomes are incubated with aromatic carboxylic acids and upon excitation at the absorption wavelength of the acid, permeation kinetics can be measured as an increase in Tb(3+) luminescence. The anions of the tested acids permeated egg phosphatidylcholine membranes only 12 (2-hydroxynicotinic acid), 66 (salicylic acid), and 155 (dipicolinic acid) times slower than the net neutral species. The anions, therefore, controlled the total permeation already at 1-2 pH units above their pK(a). These results indicate that in contrast to the expectations of the pH-partition hypothesis, lipid bilayer permeation of an acidic compound can be completely controlled by the anion at physiological pH.
Thomae
Anita V
AV
Department of Chemistry and Applied Biosciences, ETH Federal Institute of Technology, 8093 Zurich, Switzerland.
Wunderli-Allenspach
Heidi
H
Krämer
Stefanie D
SD
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D020003:1-Octanol / Q000737:chemistry; D000818:Animals; D000838:Anions; D001703:Biophysics / Q000379:methods*; D002264:Carboxylic Acids / Q000737:chemistry*; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D004531:Eggs; D006863:Hydrogen-Ion Concentration; D007477:Ions; D007700:Kinetics; D008027:Light; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008567:Membranes, Artificial; D008956:Models, Chemical; D015233:Models, Statistical; D009539:Nicotinic Acids / Q000737:chemistry; D010539:Permeability; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry; D010848:Picolinic Acids / Q000737:chemistry; D011199:Potentiometry; D020156:Salicylic Acid / Q000737:chemistry; D012542:Scattering, Radiation; D013053:Spectrophotometry; D013499:Surface Properties; D013997:Time Factors
D000838:Anions; D002264:Carboxylic Acids; D007477:Ions; D008051:Lipid Bilayers; D008081:Liposomes; D008567:Membranes, Artificial; D009539:Nicotinic Acids; D010713:Phosphatidylcholines; D010743:Phospholipids; D010848:Picolinic Acids; D015060:1,2-Dipalmitoylphosphatidylcholine; D020003:1-Octanol; D020156:Salicylic Acid; C011866:2-hydroxynicotinic acid; C004860:dipicolinic acid