The cutoff phenomenon associated with the effectiveness of long-chain alcohols in the induction of anesthesia is also observed for various antimicrobial activities, although the mechanism has remained unknown for over eight decades. The minimum inhibitory concentrations at 25°C for budding yeast growth exponentially decreased with increasing chain length of n-alcohols (C₂-C₁₂), whereas alcohols ≥C₁₃ lost the inhibitory effect. Thus, growth inhibition by n-alcohols obeys the Meyer-Overton correlation up to C₁₂ and exhibits a cutoff phenomenon. The densities of n-alcohols are low, and the melting point and hydrophobicity increase with chain length. C₁₃ and C₁₄ inhibited yeast growth at 39.8°C, above their melting points. Alcohols ≤C₁₄ inhibited thermophilic bacterial growth at 50°C, whereas C₁₆ inhibited it at 67.5°C, above their melting points. Thus, the high melting points of long-chain alcohols contribute to the cutoff phenomenon. C₁₄ did not effectively inhibit yeast growth in a static culture at 39.8°C, in contrast to a shaking culture, in which the low density-dependent concentration gradient was eliminated. The duration of the transient growth inhibition of yeast by C₁₂ was prolonged by sonication, which prevented hydrophobic aggregation. Therefore, a nonuniform distribution owing to low density and high hydrophobicity contributes to the cutoff. C₁₄ inhibited the growth at 25°C of the pdr1,3,5 mutant, defective in multidrug efflux pumps, whereas C₁₂ did not inhibit the growth of yeast overexpressing PDR5, indicating that the sensitivity to long-chain alcohols contributed to the cutoff. A balance between the physicochemical solubility of and the biological sensitivity to long-chain alcohols determines the cutoff chain length.

1964-10-01·Biochimica et Biophysica Acta (BBA) - Specialized Section on Lipids and Related Subjects

Utilization of individual non-esterified fatty acids by the isolated perfused rat heart

Article

作者: A.F. Willebrands

Rat hearts were perfused for 1 hr. in a fluid containing 1-1.5% albumin and 3-4 micromoles fatty acid/g. (Dole and Meinertz, CA 54, 24999b).An aliquot of perfusion extract was extracted with 0.05N KOH in 50% EtOH.The nonesterified fatty acids thus isolated were converted to the Me esters and these were analyzed by gas chromatography on a succinate polyester stationary phase.Dole's method (loc. cit.) (titration) could not be applied to media with very low nonesterified fatty acid contents.Therefore, the total nonesterified fatty acid concentration was calculated from the change in its percentage after the addition of a known small amount of pure C₁₆.Lipid fractions other than nonesterified fatty acids were not found in the medium.Crude oleic acid (approx. 1 millimole/l.) was used as a source of fuel for the heart.After 1 hr. perfusion, the concentration of oleic acid decreased from 69.5 to 60.3%; those of C₁₆, C₁₈, and C_18:2 increased (number of double bonds follows colon).The absolute concentration of C₁₆ increased from 23 to 29 micromoles/l.By decreasing the molar ratio C_18:1/C₁₆ the decrease in the relative concentration of C_18:1 during the perfusion gradually diminished and changed to an increase in an experiment with 80% C₁₆ and 7% C_18:1.The same phenomenon in the opposite direction occurred for the relative concentration of C₁₆.In most of these experiments the absolute concentration of C₁₈ increased during perfusion.In a series of experiments, the medium contained albumin plus glucose (11 millimoles/l.), or albumin plus pure C₁₆ (1 millimole/l.), or albumin plus pure C_18:1 (1 mole/l.).The mean increase in concentration per hr. under these conditions was approx. 10 micromoles/l. for C₁₆ and 0-5 micromoles/l. for the other acids.Experiments were made with a medium containing C₁₆, C₁₈, C_18:1, and C_18:2 in a molar ratio 1:1:1:1.The order of preference in the degree of extraction for the 4 acids was C_18:1, C_18:2, C₁₆, and C₁₈.Unsaturated fatty acids are more readily extracted by the isolated perfused rat heart than saturated acids with the same number of C atoms, with the degree of extraction decreasing with the chain length.

100 项与 C-0016 相关的药物交易

登录后查看更多信息