How fatty acids of different chain length enter and leave cells by free diffusion
Prostaglandins Leukot Essent Fatty Acids. 2006 Sep;75(3):149-59. Epub 2006 Jul 7.
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Opposing views exist as to how unesterified fatty acids (FA) enter and leave cells. It is commonly believed that for short- and medium-chain FA free diffusion suffices whereas it is questioned whether proteins are required to facilitate transport of long-chain fatty acid (LCFA). Furthermore, it is unclear whether these proteins facilitate binding to the plasma membrane, trans-membrane movement, dissociation into the cytosol and/or transport in the cytosol. In this mini-review we approach the controversy from a different point of view by focusing on the membrane permeability constant (P) of FA with different chain length. We compare experimentally derived values of the P of short and medium-chain FA with values of apparent permeability coefficients for LCFA calculated from their dissociation rate constant (k(off)), flip-flop rate constant (k(flip)) and partition coefficient (Kp) in phospholipid bilayers. It was found that Overton's rule is valid as long as k(flip)<<k(off). With increasing chain length, the permeability increases according to increasing Kp and reaches a maximum for LCFA with chain length of 18 carbons or longer. For fast flip-flop (e.g. k(flip)=15s(-1)), the apparent permeability constant for palmitic acid is very high (P(app)=1.61 cm/s). Even for a slow flip-flop rate constant (e.g. k(flip)=0.3s(-1)), the permeability constant of LCFA is still several orders of magnitude larger than the P of water and other small non-electrolytes. Since polyunsaturated FA have basically the same physico-chemical properties as LCFA, they have similar membrane permeabilities. The implications for theories involving proteins to facilitate uptake of FA are discussed.