ISSN:
1432-1424
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Chemistry and Pharmacology
Notes:
Abstract Relationships between the permeability coefficient (PHA) and partition coefficient (K m/w) of acetic acid and the surface density of DMPC:cholesterol bilayers have been investigated. Permeability coefficients were measured in large unilamellar vesicles by NMR line broadening. Bilayer surface density, σ, was varied over a range of 0.5–0.9 by changing cholesterol concentration and temperature. The temperature dependence of PHA for acetic acid exhibits Arrhenius behavior with an average apparent activation energy (E a ) of 22±3 kcal/mole over a cholesterol mole fraction range of 0.00–0.40. This value is much greater than the enthalpy change for acetic acid partitioning between bulk decane and water (ΔH° = 4.8±0.8 kcal/mole) and the calculated E a (= 8.0 kcal/mole) assuming a “bulk phase” permeability model which includes the enthalpy of transfer from water to decane and the temperature dependence of acetic acid's diffusion coefficient in decane. These results suggest that dehydration, previously considered to be a dominant component, is a minor factor in determining E a . Values of 1n PHA decrease linearly with the normalized phospholipid surface density with a slope of κ = -12.4±1.1 (r = 0.90). Correction of PHA for those temperature effects considered to be independent of lipid chain order (i.e., enthalpy of transfer from water to decane and activation energy for diffusion in bulk hydrocarbon) yielded an improved correlation (κ = -11.7±0.5 (r = 0.96)). The temperature dependence of Km/w is substantially smaller than that for PHA and dependent on cholesterol composition. Values of 1n Km/w decrease linearly with the surface density with a slope of κ = -4.6±0.3 (r = 0.95), which is 2.7-fold smaller than the slope of the plot of 1n PHA vs. σ. Thus, chain ordering is a major determinant for molecular partitioning into and transport across lipid bilayers, regardless of whether it is varied by lipid composition or temperature.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00207271
