Biological membranes lipophilicity

A close relationship exists between physicochemical properties of pigment molecules and their ability to be absorbed and thus to exhibit biological functions. Carotenoids are hydrophobic molecules that require a lipophilic environment. In vivo, they are found in precise locations and orientations within biological membranes. For example, the dihydroxycarotenoids such as lutein and zeaxanthin orient themselves perpendicularly to the membrane surface as molecular rivets in order to expose their hydroxyl groups to a more polar environment. 

In concluding this section we hope we have shown that there is a clear need for more elaborated studies to understand how lipophilic ions interact with biological membranes - an aspect that may look deceptively simple, but which is not yet completely understood. 

L. G. Reevaluating equilibrium and kinetic binding parameters for lipophilic drugs based on a structural model for drug interaction with biological membranes. 

Whereas the relationship of solute permeability with lipophilicity has been studied in a large number of in vivo systems (including intestinal absorption models [54,55], blood-brain [56 58] and blood nerve [59] barrier models, and cell culture models [60 62], to name just a few), numerous in vitro model systems have been developed to overcome the complexity of working with biological membranes [63-66]. Apart from oil-water systems that are discussed here, the distribution of a solute between a water phase and liposomes is... 

New developments in immobilization surfaces have lead to the use of SPR biosensors to monitor protein interactions with lipid surfaces and membrane-associated proteins. Commercially available (BIACORE) hydrophobic and lipophilic sensor surfaces have been designed to create stable membrane surfaces. It has been shown that the hydrophobic sensor surface can be used to form a lipid monolayer (Evans and MacKenzie, 1999). This monolayer surface can be used to monitor protein-lipid interactions. For example, a biosensor was used to examine binding of Src homology 2 domain to phosphoinositides within phospholipid bilayers (Surdo et al., 1999). In addition, a lipophilic sensor surface can be used to capture liposomes and form a lipid bilayer resembling a biological membrane. 

Carotenoids are hydrophobic molecules and thus are located in lipophilic sites of cells, such as bilayer membranes. Their hydrophobic character is decreased with an increased number of polar substitutents (mainly hydroxyl groups free or esterified with glycosides), thus affecting the positioning of the carotenoid molecule in biological membranes. For example, the dihydroxycarotenoids such as LUT and zeaxanthin (ZEA) may orient themselves perpendicular to the membrane surface as molecular rivet in order to expose their hydroxyl groups to a more polar environment. In contrast, the carotenes such as (3-C and LYC could position themselves parallel to the membrane surface to remain in a more lipophilic environment in the inner core of the bilayer membranes (Parker, 1989 Britton, 1995). Thus, carotenoid molecules can have substantial effects on the thickness, strength, and fluidity of membranes and thus affect many of their functions. 

The conformation of gramicidin in aqueous solution has been extensively studied. A lipophilic left-handed helical structure has been proposed for gramicidin A 0 1 1. it was proposed that the mode of action of gramicidin is due to the formation of ion transport channels across biological membranes. 

The studies on phospholipid bilayers with defined amounts of charged component are helpful to explain the partition characteristics in biological membranes. Liposome water partition data of propranolol in lipids from kidney epithelial cells (a common model system in pharmaceutical sciences for the uptake into the gastrointestinal tract) have been successfully described with partition models developed for pure bilayers or defined mixtures [159]. Since lipophilic cations and anions can be used as probes for the membrane potential, their interaction with microbial and mitochondrial membranes has been studied... 

Organic surfactants tend to accumulate in biological membranes due to their lipophilic alkyl chains and their affinity for interfaces. Through this characteristic, organisms are capable of concentrating surfactants. Surfactants of all classes are readily taken up across gills [1]. Therefore, it is important to dispose of techniques that make it possible to extract and quantify the analyte in biological tissues and media. 

FLORENCE ET AL. Nonionic Surfactants with Biological Membranes 197 Surfactant lipophilicity... 

All these compounds are moderately lipophilic and should show excellent ability to cross biological membranes by transcellular absorption. Propranolol, betaxolol and metoprolol all have minimal gut first-pass metabolism, as shown by the low value for E(g. i.). Metabolism and first pass effects for these compounds are largely confirmed to the liver as shown by the values for E(g. i.). In contrast talinolol shows high extraction by the gastrointestinal tract with low liver extraction [13]. These effects are illustrated graphically in Figure 3.9 which shows the bioavailability predicted from hepatic extraction contrasted with that seen in vivo in man. 

In order for a substance to be absorbed, it must cross biological membranes. Most substances cross by passive diffusion. This process requires a substance to be soluble both in lipid and water. The most useful parameters providing information on the potential for a substance to diffuse across biological membranes are the octanol/water partition coefficient (Log P) value and the water solubility. The Log value provides information on the relative solubility of the substance in water and the hydrophobic solvent octanol (used as a surrogate for lipid) and is a measure of lipophilicity. Log P values above zero indicate that the substance is more soluble in octanol than water, i.e., is lipophilic, and values below zero (negative values) indicate that the substance is more soluble in water than octanol, i.e., is hydrophilic. In general, moderate Log P values (between 0 and 4) are favorable for absorption. However, a substance with a Log P value around 0 and low water solubility (around 1 mg/1) will also be poorly soluble in lipids and hence not readily absorbed. It is therefore important to consider both the water solubility of a substance and its Log P value when assessing the potential of that substance to be absorbed. 

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