Lipids correlation with solubility

Esterbauer et al. (1991) have demonstrated that /3-carotene becomes an effective antioxidant after the depletion of vitamin E. Our studies of LDL isolated from matched rheumatoid serum and synovial fluid demonstrate a depletion of /8-carotene (Section 2.2.2.2). Oncley et al. (1952) stated that the progressive changes in the absorption spectra of LDL were correlated with the autooxidation of constituent fatty acids, the auto-oxidation being the most likely cause of carotenoid degradation. The observation that /3-carotene levels in synovial fluid LDL are lower than those of matched plasma LDL (Section 2.2.2) is interesting in that /3-carotene functions as the most effective antioxidant under conditions of low fOi (Burton and Traber, 1990). As discussed above (Section 2.1.3), the rheumatoid joint is both hypoxic and acidotic. We have also found that the concentration of vitamin E is markedly diminished in synovial fluid from inflamed joints when compared to matched plasma samples (Fairburn etal., 1992). This difference could not be accounted for by the lower concentrations of lipids and lipoproteins within synovial fluid. The low levels of both vitamin E and /3-carotene in rheumatoid synovial fluid are consistent with the consumption of lipid-soluble antioxidants within the arthritic joint due to their role in terminating the process of lipid peroxidation (Fairburn et al., 1992). 

General anesthetics are usually small solutes with relatively simple molecular structure. As overviewed before, Meyer and Overton have proposed that the potency of general anesthetics correlates with their solubility in organic solvents (the Meyer-Overton theory) almost a century ago. On the other hand, local anesthetics widely used are positively charged amphiphiles in solution and reversibly block the nerve conduction. We expect that the partition of both general and local anesthetics into lipid bilayer membranes plays a key role in controlling the anesthetic potency. Bilayer interfaces are crucial for the delivery of the anesthetics. 

Riederer, M. and Schneider, G. (1990). The effect of the environment on the permeability and composition of Citrus leaf cuticles. 2. Composition of soluble cuticular lipids and correlation with transport properties. Planta, 180, 154-165. 

The octanol solubility term is included to compensate for the difference in lipid solubility and octanol solubility of large, hydrophobic molecules, and the melting point term is intended to allow octanol solubilities for both solids and liquids to be included in the same equation. Octanol solubility is, however, highly correlated with melting point (Yalkowsky et al., 1983). 

Action on the plasma membrane is the first and most fundamental of the bewildering array of deleterious effects of the cinnamic and benzoic acids. They reduce the transmembrane electrochemical potential with the immediacy and extent of that action depending on the concentration and lipid solubility of the compound.35,37,45,60 Rate of uptake also is concentration and pH-dependent, with transfer into and across the membrane greatest with lower pH conditions and higher external concentrations.60 Phenolic acid-induced depolarization of membranes causes a nonspecific efflux of both anions and cations accompanying the increased cell membrane permeability, and these membrane effects correlate with an inhibition of ion uptake. The phenolic acids suppress absorption of phosphate, potassium, nitrate, and magnesium ions, and overall changes in tissue... 

For most conventional drag molecules, which tend to be small and lipophilic, absorption occurs transcellularly, via passive diffusion across the epithelial cells. In this case, where the GI tract (or other epithelial interface) is assumed to act as a simple lipophilic barrier, absorption occurs down a concentration gradient according to Fick s Law, and the rate of absorption correlates with the lipid solubility of the drag (see Section 1.3.3.2). 

Hydrophilic compounds may be absorbed via the paracellular route, moving between the epithelial cells via passive diffusion whereas lipid soluble drags are usually absorbed transcellularly, at rates which correlate with their lipid/water diffusion coefficients. Macromolecules may be absorbed via endocytic processes. 

Modern inhalation anesthetics are nonexplosive agents that include the gas nitrous oxide as well as a number of volatile halogenated hydrocarbons. As a group, these agents decrease cerebrovascular resistance, resulting in increased perfusion of the brain. They cause bronchodilation and decrease minute ventilation. Their clinical potency cannot be predicted by their chemical structure, but potency does correlate with their solubility in lipid. The movement of these agents from the lungs to the different body compartments depends upon their solubility in blood and various tissues. Recovery from their effects is due to redistribution from the brain. 

Log P data (octanoLwater partition coefficients and a reflection of lipid solubility) of nerve agents were used to both predict absorption through the skin and determine the distribution of OP compounds in tissues, and then correlated with toxicity as measured by the onset of fasciculation in... 

The passive permeability of lipid membranes is another fluidity related parameter. In general, two mechanisms of membrane permeability can operate in the membrane (8). For many nonpolar molecules, the predominant permeation pathway is solubility-diffusion, which is a combination of partitioning and diffusion across the bilayer, both of which depend on lipid fluidity. In a few cases, such as permeation of positively charged ions through thin bilayers, an alternative pathway prevails (9, 10). It is permeation through transient pores produced in the bilayer by thermal fluctuations. This mechanism, in general, correlates with membrane fluidity. However, for model membranes undergoing the main phase transition, permeation caused by this mechanism exhibits a clear maximum near the phase transition point (11). 

As is apparent in Fig. 3, considerable similarity exists in the arrangement of the electron transfer cofactors in PS I and PS n. The main differences between the two systems are as follows 1) PS I has three Pe4S4 iron-sulfur clusters. Ex, Ea, and Eb, located on the stromal side of the complex 2) In PS I the primary acceptor is a chlorophyll, not pheophytin and 3) the distance between the primary acceptor (Aqa3 ) and phylloquinone (Aia,b) in PS I is significantly shorter than the corresponding distance between PheoA,B and Qa.b in PS II and Type II reaction centers. These structural differences correlate with functional differences between the two types of reaction centers. In PS II, the mobile electron carrier on the stromal side of the complex is Qb, which is a lipid-soluble, two-electron acceptor. In contrast, the mobile electron carrier in PS I is ferredoxin, which is a water-soluble, one-electron acceptor. The three iron-sulfur clusters in PS I provide a chaimel by which electrons are funneled out of the reaction center to ferredoxin. On the donor side of the complex, plastocyanin, the reductant that replenishes electrons removed from P700, is also a water-soluble protein and is a one-electron donor. Thus, each photon absorbed by the PS I complex leads to the transfer of one electron from plastocyanin to ferredoxin. In Fig. 2, it is apparent that the midpoint potentials of the acceptors in PS I are about 500 to 700 mV more negative than those in PS II, and the... 

Perugini, C., Bagnati, M., Can, C., Bordone, R., Zoppis, E., PafFoni, P., Re, R., Albano, E., and Bellomo, G. (2000) Distribution of lipid-soluble antioxidants in lipoproteins from healthy subjects. I. Correlation with plasma antioxidant levels and composition of lipoproteins. Pharmacol Res 41, 55-65. 

Although the undissociated (un-ionized) form of a drug has the higher lipid solubility, the un-ionized moieties themselves have differing lipid solubilities. A common way of assessing the lipid solubility of a drug is to measure its oil-water partition coefficient. As with pH, buccal absorption has been shown to be positively correlated with a drug s oil-water partition coefficient. 

The antifungal activity of a series of salts of 9-aminoacridine and its derivatives was shown to correlate with the length of the carbon chain of the anion. The effect is thought to be related to increased lipid solubility and ion pair formation. ... 

Passive diffusion of sulfonamides into human red cells is determined by plasma dmg binding and lipid solubility. Apparent partition coefficients between chloroform and water at pH 7.4 show an almost linear relation with penetration constant for sulfonamides and a number of other acids. Penetration rates of sulfonamides into the aqueous humour and cerebrospinal fluid also correlate with partition coefficients (Fig. 5.11) moreover, as can be seen from the data in Fig. 5.12, the antibacterial effects of fatty acids and esters towards B. subtilis correlate with octanol/water partition coefficients. 

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