Albumin, plasma solubility

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. 

A type of protein which is easily digested and which contains a good proportion of the essential amino acids. It is present in the tissues and body fluids of animals and man as plasma albumin. It is also in milk, as lactalbumin, and in egg white, as egg albumin. Albumin is soluble in water, and is coagulated and solidified by heat. It is the principal type of protein in the blood, where it plays a major role in regulating the fluid flow between the blood and tissues. EHowever, lactalbumin and egg albumin provoke allergies in some people. 

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-... 

The diversity in primary, secondary, tertiary, and quaternary stmctures of proteins means that few generalisations can be made concerning their chemical properties. Some fulfil stmctural roles, such as the collagens (found in bone) and keratin (found in claws and beaks), and are insoluble in all solvents. Others, such as albumins or globulins of plasma, are very soluble in water. Still others, which form part of membranes of cells, are partly hydrophilic ( water-loving , hence water-soluble) and partly lipophilic ( lipid-loving , hence fat-soluble). 

Aqueous solubility is not usually considered a priori as a problem in the drug discovery of acidic compounds. More important issues are (i) the high serum albumin binding of stronger acids, (ii) the very low or nonexistent central nervous system penetration of stronger acids, (iii) the low volumes of distribution of acids limiting these mostly to plasma compartment targets, (iv) the possibility of formation of... 

Some of the zinc taken up by the intestinal epithelial cells is rapidly transferred to the portal plasma where it associates with albumin, a2 macroglobulin, and amino acids. About 67% of the zinc in plasma is bound to albumin, and about 3% is stored in liver (Stemlieb 1988). Soluble organozinc complexes are passively absorbed across the plasma membrane of the mucosa of the intestinal villi the soluble, nondiffusable complexes are transported in the intestinal products and excreted in feces (NAS 1979). Zinc loss from urine and sweat is usually small (Casey and Hambidge... 

Fig. 6. A highly idealized model for the plasma albumin molecule to account for the N-F transformation and its relationship to the titration anomaly, the cooperative detergent binding, and the altered solubility behavior of the low pH form. The model contains four folded amphipathic subunits, the hydrophobic surfaces being buried in the N form and exposed in the F form. Holes around the periphery of the molecule represent the 10 to 12 strong binding sites for detergent ions which are destroyed, upon isomerization, with the exposure of a large number of weaker sites. Reprinted with permission from Foster (1960). Copyright by Academic Press, Inc.

Acetoacetate and 3-hydroxybutyrate are known as ketone bodies. They are classified as fat fuels since they arise from the partial oxidation of fatty acids in the liver, from where they are released into the circulation and can be used by most if not all aerobic tissues (e.g. muscle, brain, kidney, mammary gland, small intestine) (Figure 7.7, Table 7.1). There are two important points (i) ketone bodies are used as fuel by the brain and small intestine, neither of which can use fatty acids (ii) ketone bodies are soluble in plasma so that they do not require albumin for transport in the blood. 

Most lipids are barely soluble in water, and many have amphipathic properties. In the blood, free triacylglycerols would coalesce into drops that could cause fat embolisms. By contrast, amphipathic lipids would be deposited in the blood cells membranes and would dissolve them. Special precautions are therefore needed for lipid transport in the blood. While long-chain fatty acids are bound to albumin and short-chain ones are dissolved in the plasma (see p. 276), other lipids are transported in lipoprotein complexes, of which there several types in the blood plasma, with different sizes and composition. 

Salicylic acid is a simple organic acid with a pKa of 3.0. Aspirin (acetylsalicylic acid ASA) has a pKa of 3.5 (see Table 1-3). The salicylates are rapidly absorbed from the stomach and upper small intestine yielding a peak plasma salicylate level within 1-2 hours. Aspirin is absorbed as such and is rapidly hydrolyzed (serum half-life 15 minutes) to acetic acid and salicylate by esterases in tissue and blood (Figure 36-3). Salicylate is nonlinearly bound to albumin. Alkalinization of the urine increases the rate of excretion of free salicylate and its water-soluble conjugates. 

In vivo studies were also conducted by several researchers. Anraku et al. (2009) examined the antioxidant effects of water-soluble chitosan in normal subjects by measuring the reduction of indices of oxidative stress. Treatment with chitosan for 4weeks produced a significant decrease in levels of plasma glucose and the atherogenic index, and led to an increase in high-density lipoprotein cholesterol (HDL-C). Chitosan treatment also lowered the ratio of oxidized to reduced albumin and increased total plasma antioxidant activity. Further, Anraku et al. (2011) proved the antioxidant effects of high MW chitosan in normal volunteers, and the obtained results were consistent with previous results observed by Anraku et al. (2009). 

In vertebrates, free fatty acids (unesterified fatty acids, with a free carboxylate group) circulate in the blood bound noncovalently to a protein carrier, serum albumin. However, fatty acids are present in blood plasma mostly as carboxylic acid derivatives such as esters or amides. Lacking the charged carboxylate group, these fatty acid derivatives are generally even less soluble in water than are the free fatty acids. 

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. 

Z Uptake of bilirubin by the liven Bilirubin is only slightly soluble in plasma and, therefore, is transported to the liver by binding non-covalently to albumin. [Note Certain anionic drugs, such as salicylates and sulfonamides,1 can displace bilirubin from abu-min, permitting bilirubin to enter the central nervous system (CNS). This causes the potential for neural damage in infants.] Bilirubin dissociates from the carrier albumin molecule and enters a hepatocyte, where it binds to intracellular proteins, particularly the protein ligandin. 

Albumin is the most abundant protein in human and other animal plasma. It is estimated that up to 40% of the total albumin in humans is in circulation transporting essential nutrients, especially those that are sparingly soluble in aqueous-based plasma. For example, the fatty acids, which are important fuel molecules for the peripheral tissue, are distributed by albumin. In addition, albumin is the plasma transport protein for other substances including bilirubin, thyroxine, and steroid hormones. Also, many drugs including aspirin, sulfanilamides, clofibrate, and digitalis bind to albumin and are most likely carried to their sites of action by the protein. 

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