title: How fatty acids of different chain length enter and leave cells by free diffusion.
abstract: 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.
authors.affiliation: Laboratory of Alzheimer's and Parkinson's Disease Research, Institute of Metabolic Biochemistry, Ludwig-Maximilians-University, Schillerstrasse 44, D-80336 Munich, Germany. fkamp@med.uni-muenchen.de
authors.forename: Frits
authors.initials: F
authors.lastname: Kamp
authors.forename: James A
authors.initials: JA
authors.lastname: Hamilton
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002463:Cell Membrane Permeability / Q000502:physiology*; D004058:Diffusion; D005230:Fatty Acids, Nonesterified / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism
chemical_list: D005230:Fatty Acids, Nonesterified; D008051:Lipid Bilayers; D010743:Phospholipids