Proton/hydroxide conductance through phospholipid bilayer membranes: effects of phytanic acid.
Mechanisms of proton/hydroxide conductance (GH/OH) were investigated in planar (Mueller-Rudin) bilayer membranes made from decane solutions of phospholipids or phospholipids plus phytanic acid (a 20-carbon, branched chain fatty acid). At neutral pH, membranes made from diphytanoylphosphatidylcholine or bacterial phosphatidylethanolamine had GH/OH values in the range of (2-5) X 10(-9) S X cm-2, corresponding to H+/OH- 'net' permeabilities of about (0.4-1.0) X 10(-5) cm X s-1. GH/OH was inhibited by serum albumin, phloretin, glycerol and low pH, but was increased by chlorodecane and voltage greater than 80 mV. Water permeability and GH/OH were not correlated, suggesting that water and H+/OH- cross the membrane by separate pathways. Addition of phytanic acid to the phospholipids caused an increase in GH/OH which was proportional to the first power of the phytanic acid concentration. In membranes containing phytanic acid, GH/OH was inhibited by albumin, phloretin, glycerol and low pH, but was increased by chlorodecane and voltages greater than 80 mV. The results suggest that phytanic acid acts as a simple (A- type) proton carrier. The qualitative similarities between the behavior of GH/OH in unmodified and phytanic-acid containing membranes suggest that phospholipids may contain weakly acidic contaminants which cause most of GH/OH at pH greater than 4. However, there is also a significant background (pH independent) GH/OH which may be due to hydrogen-bonded water chains. The ability of phytanic acid to act as a proton carrier may help to explain the toxicity of phytanic acid in Refsum's disease, a metabolic disorder in which phytanic acid accumulates to high levels in plasma, cells and tissues.
D002463:Cell Membrane Permeability / Q000187:drug effects; D004058:Diffusion; D004537:Eicosanoic Acids / Q000494:pharmacology*; D004553:Electric Conductivity; D005990:Glycerol / Q000494:pharmacology; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D006878:Hydroxides / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism*; D010693:Phloretin / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D010831:Phytanic Acid / Q000494:pharmacology*; D011522:Protons; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014867:Water / Q000378:metabolism
D004537:Eicosanoic Acids; D006843:Hydrocarbons, Chlorinated; D006878:Hydroxides; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D011522:Protons; D014867:Water; D010831:Phytanic Acid; D012710:Serum Albumin, Bovine; C021016:1,2-diphytanoylphosphatidylcholine; D005990:Glycerol; D010693:Phloretin