engleski

Saturated Fatty Acids with Different Lengths in DOPC Phospholipid Bilayers - Free Energy and Apparent pKa Calculations

Long chain fatty acids (LCFA) are important nutrients which regulate the storage and energy resources in living systems. LCFAs can diffuse through phospholipid bilayers and affect the biophysical properties of the mitochondrial inner membrane by increasing H+ conductance across the phospholipid bilayer [1]. LCFAs activate uncoupling proteins (UCPs) embedded in biological membranes – in particular, FAs increase the UCP1 and UCP2 dependent H+ leak. In order to understand the details of the H+ transport, we considered neutral and deprotonated form of three LCFA with different lengths: myristic (C14:0), palmitic (C16:0) and stearic (C20:0) acid in dioleoyl-sn-glycero-3- phosphocholine (DOPC) bilayer. We calculated free energy profiles using all atom molecular dynamic (MD) simulation using umbrella sampling technique. Free energy profiles suggest that neutral forms of LCFA are located deeper in DOPC bilayer than deprotonated forms and stabilization inside the bilayer increases with the chain length for both neutral and deprotonated forms. On the other hand, free energies of flip-flop of both neutral and anionic forms are constant upon the prolongation of the fatty acid. Based on the free energy curves, we also calculated apparent fatty acid pKa, app values in the bilayer which are 7.0, 7.2 and 6.3 for myristic, palmitic and stearic acid and are increased by several pKa units compared to the corresponding pKa values in water. We found that spontaneous protonation of fatty acid anions takes place in the bilayer interior at ca. 1.4 nm from the bilayer center for all studied fatty acids. Presented results are one step in the clarification of mechanism of the H+ transport and will help in future studies across more realistic biological membranes.

long chain fatty acids ; proton tranfer

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