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.