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2.B.35.  The Fatty Acid-mediated Proton Transport (FA-PT) Family 

Fatty acids transfer protons across lipid layers faster than unassisted proton diffusion (Hamilton 2007). The length of the fatty acid plays a role in determining the transmembrane properties of fatty acids (Pohl et al. 2004). The length-dependent diffusion rates across lipid membranes are thought to relate to the effective van der Waals interactions between the alkyl chains of the fatty acids and the phospholipids (Milger et al. 2006). Biophysical properties of long chain fatty acids (LCFA) in membranes allow fast free diffusion by a “flip-flop” mechanism in the phospholipid bilayer (Hamilton 2007).

“Flip-flop” i.e., the complete movement of the FA across the bilayer with reorientation of the headgroup to the interface) via the uncharged form without catalysis by a protein has been demonstrated. The presence of this form in the membrane achieves a high flux down the concentration gradient across the membrane without movement of the charged form. LCFA might be able to move back and forth across the bilayer (“flip-flop” i.e., the complete movement of the FA across the bilayer with reorientation of the headgroup to the interface) via the uncharged form without catalysis by a protein. The presence of this form in the membrane would achieve a high flux down the concentration gradient across the membrane without movement of the charged form. Un-ionized LCFA has a low energy barrier for translocation compared to the ionized form.This gives rise to transmembrane proton transport (Hamilton 2007).

Conclusions of several studies suggest that (i) FAs can permeate a plasma membrane by diffusion; (ii) membrane transport is mainly a biophysical process that occurs in the presence or absence of metabolism; (iii) all types of FAs are accessible to the interior of the cell, and (iv) FAs can exit a cell rapidly. With increasing chain length, the permeability increases according to the increasing Kp and reaches a maximum for LCFA with chain lengths of 18 carbons or longer. For fast flip-flop (e.g. kflip=15 s−1), the apparent permeability for palmitic acid is very high (Papp=1.61 cm/s) (Hamilton 2007).

The generalized carrier-type diffusion-mediated transport of protonated fatty acids is:

protonated fatty acid (out) → fatty anion + H+ (in)

References associated with 2.B.35 family:

Hamilton, J.A. (2007). New insights into the roles of proteins and lipids in membrane transport of fatty acids. Prostaglandins Leukot Essent Fatty Acids 77: 355-361. 18032007
Milger, K., T. Herrmann, C. Becker, D. Gotthardt, J. Zickwolf, R. Ehehalt, P.A. Watkins, W. Stremmel, and J. F├╝llekrug. (2006). Cellular uptake of fatty acids driven by the ER-localized acyl-CoA synthetase FATP4. J Cell Sci 119: 4678-4688. 17062637
Pohl, J., A. Ring, T. Hermann, and W. Stremmel. (2004). Role of FATP in parenchymal cell fatty acid uptake. Biochim. Biophys. Acta. 1686: 1-6. 15522816