Permeability coefficient lipid solubility/membranes

The solubility-diffusion theory assumes that solute partitioning from water into and diffusion through the membrane lipid region resembles that which would occur within a homogeneous bulk solvent. Thus, the permeability coefficient, P, can be expressed as... 

Gryns (1896), Hedin (1897), and especially Overton (1900) looked at the permeability of a wide range of different compounds, particularly non-electrolytes, and showed that rates of penetration of solutes into erythrocytes increased with their lipid solubility. Overton correlated the rate of penetration of the solute with its partition coefficient between water and olive oil, which he took as a model for membrane composition. Some water-soluble molecules, particularly urea, entered erythrocytes faster than could be attributed to their lipid solubility—observations leading to the concept of pores, or discontinuities in the membrane which allowed water-soluble molecules to penetrate. The need to postulate the existence of pores offered the first hint of a mosaic structure for the membrane. Jacobs (1932) and Huber and Orskov (1933) put results from the early permeability studies onto a quantitative basis and concluded molecular size was a factor in the rate of solute translocation. 

The partition coefficient, which will be described in more detail later in this chapter, is the relative solubility of the compound in lipid and water, and the compound s solubility really reflects the ability of the toxicant to move from a relatively aqueous environment across a lipid membrane. It is this factor that is often manipulated in pesticide and drug formulations to create a vehicle. Membrane permeability is therefore strongly correlated to the lipid solubility of the toxicant in the membrane as well as... 

The permeability, P (P = Pc x D), of a nonpolar substance through a cell membrane is dependent on two physicochemical factors (1) solubility in the membrane (Pc), which can be expressed as a partition coefficient of the drug between the aqueous phase and membrane phase, and (2) diffusivity or diffusion coefficient (D), which is a measure of mobility of the drug molecules within the lipid. The latter may vary only slightly among toxicants, but the former is more important. Lipid solubility is therefore one of the most important determinants of the pharmacokinetic characteristics of a chemical, and it is important to determine whether a toxicants is readily ionized or not influenced by pH of the environment. If the toxicant is readily ionized, then one needs to understand its chemicals behavior in various environmental matrices in order to adequately assess its transport mechanism across membranes. 

Capillaries in the Brain (the Blood-Brain Barrier). Capillaries in the brain are less permeable than capillaries in other tissues. This limited permeability, which is frequently called the blood-brain barrier, is essential for brain function. Reduced permeation provides a buffer that maintains a constant brain extracellular environment, even at times when blood chemistry is changing. The basis for this lower permeability is the relative paucity of pores in the brain endothelium. Therefore, molecules that move from blood to brain must diffuse through the endothelial cell membranes. As expected from this observation, the permeability of brain capillaries depends on the size and lipid solubility of the solute. In general, molecules that are larger than several hundred in molecular weight do not permeate into the brain. Empirical relationships between cerebrovascular permeability and the oil / water partition coefficient have been developed [26] (see Figure 5.27) ... 

In this section we will restrict our discussion to small polar (oihwater partition coefficient A eUier 0.003) nonelectrolytes. However, before discussing this question in detail, it is worth noting that the value of the permeability coefficient of membranes for a large lipophilic molecule is determined by the molecule lipid solubility, its chemical nature, its molecule size and shape, and the number of hydrogen bonds (TVh) form with water. The permeability coefficient... 

Here the problem is to decide whether these solutes permeate by dissolution in the membrane fabric or by crossing the membrane through polar pathways aqueous pores . It is worth pointing out from the start that there is no conclusive evidence which enables one to decide unequivocally between these two possibilities. As will become clearer by the end of this discussion, the data at hand in certain cases (such as mammalian red cells) are merely more consistent with the postulate that these molecules permeate partly through polar pathways and not entirely by dissolution in the membrane fabric. Probably the strongest evidence for this hypothesis is summarized in Table 4. The values of the diffusional permeability coefficient for egg lecithin spherical bilayers are included in the table for comparison. Based on their lipid solubility these molecules should be quite impermeable. In fact, in certain... 

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