Hydrophobic/hydrophilic amino acids

Practically motivated, the aim was to develop methods for recovery and determination of amino acids in the context of analytical chemistry and biotechnology. Amino acids are hydrophilic compounds, which therefore are difficult targets for conventional solvent extraction. Extraction to an organic solvent may be enhanced by the addition of lipophilic cationic or anionic extractants, forming extractable complexes with amino acids, or by the use of macrocyclic compounds, which form stable hydrophobic host-guest complexes. The most popular reagents from the latter group are crown... 

As another example of polarity effects on macromo-lecular structure, consider polypeptide chains, which usually contain a mixture of amino acids with hydrophilic and hydrophobic side chains. Enzymes fold into complex three-dimensional globular structures with hydrophobic residues located on the inside of the structure and hydrophilic residues located on the surface, where they can interact with water (fig. 1.12). 

The extrinsic pathway of coagulation is activated when circulating factor VII encounters tissue factor. Tissue factor is a transmembrane glycoprotein, which is normally expressed by subendothelial fibroblast-like cells, which surround the blood vessel. An intact endothelium normally shields the circulating blood from exposure to tissue factor. The tissue factor molecule consists of a 219 amino acid hydrophilic extracellular domain, a 23 amino acid hydrophobic region that spans the membrane, and a 21 amino acid cytoplasmic tail that anchors the molecule to the cell membrane (15,16). Other sites of tissue factor expression include activated monocytes, activated endothelial cells, and atherosclerotic plaques. 

Proteins are made from many amino acids with hydrophilic and hydrophobic side chains. The main principle is that amino acids with hydrophobic side chains tend to be in the core of a protein, while the hydrophilic side chains lie on the exterior. The hydrophilic tendencies of carbonyl and amino groups in the backbone of the protein are neutralized by hydrogen bonding, such as in a helices (see Chapter 12). 

Fig. 9. A representation of the conformational and surface changes in RmL during interfacial activation the shaded amino acids are hydrophilic, others are hydrophobic. The cylinder represents the lid, rolling in the direction shown by the arrows, across the molecular surface. The active center is labeled.

Hydrophilic (water-loving) and hydrophobic (water-fearing) refer to the polarity of the R groups. When the R group consists of a polar group, then the amino acid is hydrophilic. When the R group consists of a nonpolar group, then the amino acid is hydrophobic. 

It is worto noting that all toe amino acid-diacefylene lipid microstructures studied here could be polymerizable to form blue colored PDAs. However, only hydrophilic amino acid lipids can readily form bilayer vesicles and allow polymerization (77). The intensity of toe initial blue color, however, varies with headgroups. Amino acids with hydrophilic segments give toe darkest blue appearance, while hydrophobic amino acids (lie-) produce barely noticeable blue appearance. 

Figure 10.7 A diagrammatic representation of modes of binding of an anionic surfactant to a protein, after Dominguez [43]. Some modes of interaction, especially hydrophobic interactions with the amino acid hydrophobic residues would be equally appropriate for non-ionic and cationic surfactants. In addition, cationic surfactants could attach themselves electrostatically to the anionic sites. The hydrophobic interactions are supported by the results of Helenius and Simons [44] which demonstrated that lipophilic proteins bound up to about 70% of their weight of deoxycholate and Triton X-lOO but that hydrophilic proteins bound little surfactant.

A tertiary structure is stabilized by interactions that push amino acids with hydrophobic R groups to the center and pull amino acids with hydrophilic R groups to the surface, and by interactions between amino acids with R groups that form hydrogen bonds, disulfide bonds, and salt bridges. 

The most common location for an a helix in a protein structure is along the outside of the protein, with one side of the helix facing the solution and the other side facing the hydrophobic interior of the protein. Therefore, with 3.6 residues per turn, there is a tendency for side chains to change from hydrophobic to hydrophilic with a periodicity of three to four residues. Although this trend can sometimes be seen in the amino acid sequence, it is not strong enough for reliable stmctural prediction by itself, because residues that face the solution can be hydrophobic and, furthermore, a helices can be either completely buried within the protein or completely exposed. Table 2.1 shows examples of the amino acid sequences of a totally buried, a partially buried, and a completely exposed a helix. 

Figure 3.6 Four-helix bundles frequently occur as domains in a proteins. The arrangement of the a helices is such that adjacent helices in the amino acid sequence are also adjacent in the three-dimensional structure. Some side chains from all four helices are buried in the middle of the bundle, where they form a hydrophobic core, (a) Schematic representation of the path of the polypeptide chain in a four-helrx-bundle domain. Red cylinders are a helices, (b) Schematic view of a projection down the bundle axis. Large circles represent the main chain of the a helices small circles are side chains. Green circles are the buried hydrophobic side chains red circles are side chains that are exposed on the surface of the bundle, which are mainly hydrophilic.

Lesk and Chothia did find, however, that there is a striking preferential conservation of the hydrophobic character of the amino acids at the 59 buried positions, but that no such conservation occurs at positions exposed on the surface of the molecule. With a few exceptions on the surface, hydrophobic residues have replaced hydrophilic ones and vice versa. However, the case of sickle-cell hemoglobin, which is described below, shows that a charge balance must be preserved to avoid hydrophobic patches on the surface. In summary, the evolutionary divergence of these nine globins has been constrained primarily by an almost absolute conservation of the hydro-phobicity of the residues buried in the helix-to-helix and helix-to-heme contacts. 

Since the outside of the barrel faces hydrophobic lipids of the membrane and the inside forms the solvent-exposed channel, one would expect the P strands to contain alternating hydrophobic and hydrophilic side chains. This requirement is not strict, however, because internal residues can be hydrophobic if they are in contact with hydrophobic residues from loop regions. The prediction of transmembrane p strands from amino acid sequences is therefore more difficult and less reliable than the prediction of transmembrane a helices. 

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