On the mechanism of transbilayer transport of phosphatidylglycerol in response to transmembrane pH gradients.

Previous work [Hope et al. (1989) Biochemistry 28, 4181-4187] has shown that asymmetric transmembrane distributions of phosphatidylglycerol (PG) in PG-phosphatidylcholine (PC) large unilamellar vesicles can be induced in response to transbilayer pH gradients (delta pH). Here the mechanism of PG transport has been investigated. It is shown that PG movement in response to delta pH is consistent with permeation of the uncharged (protonated) form and that the half-time for transbilayer movement of the uncharged form can be on the order of seconds at 45 degrees C. This can result in rapid pH-dependent transmembrane redistributions of PG. The rate constant for transbilayer movement exhibits a large activation energy (31 kcal/mol) consistent with transport of neutral dehydrated PG where dehydration of the (protonated) phosphate presents the largest barrier to transmembrane diffusion. It is shown that acyl chain saturation, chain length, and the presence of cholesterol modulate the rate constants for PG transport in a manner similar to that observed for small nonelectrolytes.