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Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2018

AutorInnen: Pashkovskaya, AA; Vazdar, M; Zimmermann, L; Jovanovic, O; Pohl, P; Pohl, EE

Titel: Mechanism of Long-Chain Free Fatty Acid Protonation at the Membrane-Water Interface.

Quelle: Biophys J. 2018; 114(9):2142-2151



Autor/innen der Vetmeduni Vienna:

Jovanovic Olga
Pashkovskaya Alina
Pohl Elena
Zimmermann Lars

Beteiligte Vetmed-Organisationseinheiten
Institut für Physiologie, Pathophysiologie und Biophysik, Abteilung für Physiologie und Biophysik


Zugehörige(s) Projekt(e): Mechanismus der Nukleotide-vermittelten Inhibierung mitochondrialer Entkopplerproteine


Abstract:
Long-chain free fatty acids (FFAs) play an important role in several physiological and pathological processes such as lipid fusion, adjustments of membrane permeability and fluidity, and the regulation of enzyme and protein activities. FFA-facilitated membrane proton transport (flip-flop) and FFA-dependent proton transport by membrane proteins (e.g., mitochondrial uncoupling proteins) are governed by the difference between FFA's intrinsic pKa value and the pH in the immediate membrane vicinity. Thus far, a quantitative understanding of the process has been hampered, because the pKa value shifts upon moving the FFA from the aqueous solution into the membrane. For the same FFA, pKa values between 5 and 10.5 were reported. Here, we systematically evaluated the dependence of pKa values on chain length and number of double bonds by measuring the ζ-potential of liposomes reconstituted with FFA at different pH values. The experimentally obtained intrinsic pKa values (6.25, 6.93, and 7.28 for DOPC membranes) increased with FFA chain length (C16, C18, and C20), indicating that the hydrophobic energy of transfer into the bilayer is an important pKa determinant. The observed pKa decrease in DOPC with increasing number of FFA double bonds (7.28, 6.49, 6.16, and 6.13 for C20:0, C20:1, C20:2, and C20:4, respectively) is in line with a decrease in transfer energy. Molecular dynamic simulations revealed that the ionized carboxylic group of the FFAs occupied a fixed position in the bilayer independent of chain length, underlining the importance of Born energy. We conclude that pKa is determined by the interplay between the energetic costs for 1) burying the charged moiety into the lipid bilayer and 2) transferring the hydrophobic protonated FFA into the bilayer.Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Keywords Pubmed: Cell Membranechemistrymetabolism
Fatty Acids, Nonesterifiedchemistrymetabolism
Hydrogen-Ion Concentration
Molecular Conformation
Molecular Dynamics Simulation
Protons
Surface Properties
Unilamellar Liposomeschemistrymetabolism
Waterchemistry

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