Lipoproteins physicochemical properties

Table 11 Physicochemical Properties and Composition of Human Lipoproteins... 

A new quality in the analysis of hydrophobically post-translational modified proteins could be achieved by the construdion of lipidated proteins in a combination of bioorganic synthesis of activated lipopeptides and bacterial expression of the protein backbone as described before. The physicochemical properties of such artificial lipoproteins differ substantially from those of the corresponding lipopeptides. The pronounced dominance of the hydrophilic protein moiety (e.g. for the Ras protein 181 amino acids) over a short lipopeptide with one or two hydrophobic modifications keeps the construct soluble up to 1CT4 M, while the biotinylated or fluorescence labeled lipopeptides exhibit low solubility in aqueous solutions and can be applied in the biophysical experiments only in vesicle integrated form or dissolved in organic solvent. 

However, the identification of increasingly lipophilic lead molecules, the physicochemical properties of which (low aqueous solubility and high log Ps) suggest a natural predisposition for increased plasma lipoprotein binding, has increased interest in the possible pharmacokinetic, therapeutic, and toxicological ramifications of drug binding to plasma lipoproteins. 

The elucidation of the structure of any lipoprotein, i.e., the organization of the protein and lipid components, is a challenging problem, because it relies on several techniques that give only partial and approximate information. Structural models should be consistent with experimental data that characterize the physiological role and the physicochemical properties of the lipoprotein and its components. Considerable effort has been expended to fit experimental data to structural models of mammalian lipoproteins (Zilversmit, 1965 Sata et al., 1972 Schneider et al., 1973 Havel, 1975 Verdery and Nichols, 1975 Shen et al., 1977 ... 

The metabolism of lipid emulsions has long been considered to be similar to that of chylomicrons with intravascular lipolysis by lipoprotein lipase (LPL) being followed by tissue uptake of remnant particles. However, other studies have suggested that lipid emulsions are cleared from blood with less lipolysis than chylomicrons and that a substantial number of emulsions can be cleared as almost intact whole particles by different tissues. The metabolism of lipid emulsions is affected by many factors, including triglyceride (TG) composition. For example, MCT LCT emulsions are cleared faster from blood than pure LCT emulsions. Recently, it was reported that pure FO emulsion particles are removed from blood faster and by different pathways as compared with LCT emulsions. Removal of LCT emulsions is modulated by LPL, apolipoprotein E (apoE), LDL receptor (LDL-R), and lactoferrin-sensitive pathways. In contrast, clearance of FO emulsions relies on LPL to a much lesser extent and is apparently independent of apoE, LDL-R, and lactoferrin-sensitive pathways. It can therefore be noted that the materials selecteds to develop a nanoemulsion composition may not only affect the physicochemical properties and stability of the formulation but may alter significantly the biofate and efficacy of the nanoemulsions. 

Owens, M.D., Baillie, G., and Halbert, G.W. 2001. Physicochemical properties of microemulsion analogues of low density lipoprotein containing amphiphatic apoprotein B receptor sequenees. Int. J. Pharm., 228, 109-117. 

After arrival in the systemic circulation the drag is released from the chylomicrons, either due to hydrolysis of the triglycerides (by the lipoproteinic lipases of the blood), or by diffusion of the drag from an intact chylomicron to the water of the plasma. For these reasons, the possibility of a drag being transported via the lymph depends on the physicochemical properties of the administered drag, as well as the quantity and the properties of the co-administered lipid carrier which is used to induce the intracellular production of chylomicrons. 

Although lipids and lipid-based formulations cannot promote drug association with intestinal lipoproteins in the absence of the requisite physicochemical dmg properties, lipid-based delivery systems can have an appreciable effect on the extent of drug absorption into the enterocyte as described in the previous section. The eventual extent of lymphatic drug transport therefore is the product of the sequential processes of drug diffusion and dissolution in the GIT, drug absorption and metabolism within the enterocyte, and partition of the drug mole-... 

Qualitative and the quantitative analyses of food allergens are essential because of the health risk they pose to food consumers (particularly to those who suffer from allergenic hypersensitivity). As most allergens are proteins, glyco- or lipoproteins, traditional protein determination assays can help examine their biochemical properties. Classical methods used for studying proteins include Physicochemical methods... 

One of the most intriguing features of lipophorin composition is the large variation in lipid content and composition that can be accommodated without modifications in the apolipoprotein composition of the particles (Table I). This feature makes lipophorin a good system in which to analyze the structure of lipoproteins and the physicochemical factors that govern their structure and properties. In addition to the previously discussed data on the size and shape of lipophorins, several studies on other aspects of lipophorin structure have been performed and need to be discussed before describing models for lipophorin structure. 

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