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.