Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2778441 | Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA) | 2006 | 11 Pages |
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 (koff), flip-flop rate constant (kflip) and partition coefficient (Kp) in phospholipid bilayers. It was found that Overton's rule is valid as long as kflip≪koff. 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. kflip=15 s−1), the apparent permeability constant for palmitic acid is very high (Papp=1.61 cm/s). Even for a slow flip-flop rate constant (e.g. kflip=0.3 s−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.