Proton/hydroxide conductance through phospholipid bilayer membranes: effects of phytanic acid

Abstract

Mechanisms of proton/hydroxide conductance ( G H/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 G H/OH values in the range of (2–5) · 10 −9 S · cm −2 , corresponding to H +/OH − ‘net’ permeabilities of about (0.4–1.0) · 10 −5 cm · s −1 . G H/OH was inhibited by serum albumin, phloretin, glycerol and low pH, but was increased by chlorodecane and voltage > 80 mV . Water permeability and G H/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 G H/OH which was proportional to the first power of the phytanic acid concentration. In membranes containing phytanic acid, G H/OH was inhibited by albumin, phloretin, glycerol and low pH, but was increased by chlorodecane and voltages > 80 mV . The results suggest that phytanic acid acts as a simple (A − type) proton carrier. The qualitative similarities between the behavior of G H/OH in unmodified and phytanic-acid containing membranes suggest that phospholipids may contain weakly acidic contaminants which cause most of G H/OH at pH > 4 . However, there is also a significant background (pH independent) G H/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.