Blood protein solubility

Water-soluble compounds are naturally easily transported in the blood. Non-soluble compounds are usually transported bound to plasma proteins (albumins). This binding is reversible in most cases but may vary remarkably. The degree of protein binding may vary between 50% and 99%. The proportion of the free (unbound) compound in the circulation is the amount of the compound that can reach the tissues and thus the target organs. Very lipid-... 

Transport in blood Bound to carrier proteins Soluble in plasma Bound to carrier proteins Soluble in plasma... 

Belgorodsky B, Fadeev L, Kolsenik J, Gozin M (2006) Formation of a soluble stable complex between pristine C60-fullerene and a native blood protein. Chembiochem 7 1783-1789. 

Some 100 different proteins occur in human blood plasma. Based on their behavior during electrophoresis (see below), they are broadly divided into five fractions albumins and ai-, tt2-, P- and y-globulins. Historically, the distinction between the albumins and globulins was based on differences in the proteins solubility -albumins are soluble in pure water, whereas globulins only dissolve in the presence of salts. 

The proteins at the heart of the humoral immune response are soluble proteins called antibodies or immunoglobulins, often abbreviated Ig. Immunoglobulins bind bacteria, viruses, or large molecules identified as foreign and target them for destruction. Making up 20% of blood protein, the immunoglobulins are produced by B lymphocytes, or B cells, so named because they complete their development in the feone marrow. 

As hormone-sensitive lipase hydrolyzes triacylglyc-erol in adipocytes, the fatty acids thus released (free fatty acids, FFA) pass from the adipocyte into the blood, where they bind to the blood protein serum albumin. This protein (Mv 66,000), which makes up about half of the total serum protein, noncovalently binds as many as 10 fatty acids per protein monomer. Bound to this soluble protein, the otherwise insoluble fatty acids are carried to tissues such as skeletal muscle, heart, and renal cortex. In these target tissues, fatty acids dissociate from albumin and are moved by plasma membrane transporters into cells to serve as fuel. 

Fig. 6.2. Model for how FcRn rescues IgG from catabolism by recycling and transcytosis. IgG and many other soluble proteins are present in extracellular fluids. Vascular endothelial cells are active in fluid phase endocytosis of blood proteins. Material taken up by these cells enters the endosomes where FcRn is found as an integral membrane protein. The IgG then binds FcRn in this acidic environment. This binding results in transport of the IgG to the apical plasma membrane for recycling into the circulation, or to the basolateral membrane for transcytosis into the extracellular space. Exposure to a neutral pFI in both locations then results in the release of IgG. The remaining soluble proteins are channeled to the lysosomal degradation pathway.

Antibodies (immunoglobulins) constitute the gamma globulin part of the blood proteins. They are soluble proteins secreted by the plasma offspring (clones) of activated B-cells. 

Figure 2.12. Schematic of dmgs binding to proteins. Soluble proteins (such as blood plasma proteins) usually have a largely hydrophilic shell with some hydrophobic patches and crevices to which hydrophobic drag molecules will tend to bind. Albumin is the single most important protein contributing to drag binding.

Accident dosimetry using biological systems in which the quantification of chromosome aberrations or the ratios between different blood proteins can give an indication of exposure, is hampered by the individual characteristics of the victim (i.e. general health, diet etc.), and by the complexity of the techniques. These problems can be avoided by adopting a more physical approach, and both chemiluminescence and thermoluminescence of possible dosimeters, for example, have been found to be useful. The drawbacks here concern the solubility with chemiluminescence, the amount of sample required for thermoluminescence, and the impossibility of taking repeated measurements with either system. In contrast, electron spin resonance (ESR) spectroscopy is not subject to these constraints. Measurement is made directly on the sample, very small amounts of material can be used, and repeated measurements are possible... 

Attempts at changing the fate of compounds in vivo by means of carbohydrate modification are not confined to EPO. For example, it has been reported that new functional characteristics (e. g., prolonged half-life in blood, improved solubility in water, etc.) can be achieved by attaching carbohydrates to particular positions of compounds, e. g., thrombopoietin with only 0-linked carbohydrate [32] and insulin without any carbohydrates [33,34]. Thus, carbohydrate modification is being acknowledged as a useful technique for modifying the functions of proteins. 

As a result of the contact of blood with none-ndothelial surfaces, several humoral and cellular systems can be activated. Exposure of blood proteins and cells to blood contacting medical devices can activate plasma proteolytic systems (coagulation (blood clotting system), fibrinolysis (process by which clot is broken down), complement cascade (a system of soluble proteins involved in microbiocidal activity and the release of inflammatory components), Kallekrein-kinin and contact systems) and at least three cellular elements (leukocytes, endothelial cells, and platelets). Contrary to the normal situations whereby these mechanisms are localized and intended to promote wound healing, activation of these systems by medical devices can result in nonlocalized systemic reactions. The preclinical and clinical assessments of hemocompatibility are designed to minimize modification of these systems. 

The most abrmdant protein in the blood is albumin, making up about 55% of the blood protein. Albumin contributes to the osmotic pressure of the blood simply because it is a dissolved molecule. It also serves as a nonspecific transport molecule for important metabolites that are otherwise poorly soluble in water. Among the molecules transported through the blood by albumin are bilirubin (a waste product of the breakdown of hemoglobin), Ca +, and fatty acids (organic anions). 

Another common chemical additive utilized to reduce protein solubility is small, polar organic molecules such as methanol, ethanol, and acetone. Such water-miscible solvents are often called anti-solvents. The most widely known separation utilizing such solvents is the Cohn method of blood fractionation, which utilizes ethanol for the recovery of a variety of proteins from blood (Cohn et al. 1940). Such separations are usually carried out near the isoelectric point in order to bring the protein to a point of minimal solubility and minimize the amount of anti-solvent required to achieve the precipitation or crystallization. 

Yildiz H, Akyilmaz E, Din9kaya E (2004) Catalase immobilization in cellulose acetate beads and determination of its hydrogen peroxide decomposition level by using a catalase biosensor. J Artif Cells Blood Subst Biotechnol 32(3) 443 52 Yu M, de Swaan Arons J, Smit JA (1994). A simple model for estimating protein solubility in aqueous polymer solutions. J Chem Technol Biotechnol 60(4) 413 18... 

H) Collagen derived from the same species as recipient Tissues derived from the same species, for example, tissue grafts for medical use derived from human cadaveric donors, are referred to as allografts. These tissues constitute a plentiful source of stmctural materials for use in surgical repair of the musculoskeletal system. In contrast to vital organs for transplantation that are utilized without modification, stmctural tissues such as bone and soft connective tissues must be processed to remove blood, cells, soluble proteins, and enzymes before they can be used in vivo. Allografts retain many of their intrinsic stmctural and biomechanical properties. 

Initial work on radiolabeling of autologous polymorphonuclear leukocytes was performed by McAfee and Thakur [30]. One of the compounds they examined was the nonpolar, lipid-soluble complex 8-hydroxyquinoline (oxine) (Fig. 2). Indium forms a neutral, lipid-soluble complex with oxine which will penetrate cellular membranes. Subsequently, studies showed that this technique could be used to label leukocytes and platelets with retention of biological activity [31]. After diffusing intracellularly, the ln-oxine complex dissociates and the " In is bound to nuclear and cytoplasmic proteins (Fig. 3) [32-34]. Due to the high stability of indium with the blood protein transferrin, it is necessary to label platelets or WBCs in the absence of plasma. In addition, a final wash of the labeled cells using plasma will remove any loosely bound indium by complexation with transferrin [35,36]. 

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