Acidic and Basic Side Chains

It is interesting to note that the amino acid side chains may be either neutral as in valine, acidic as in glutamic acid or basic as in lysine. The presence of both acidic and basic side chains leads to proteins such as casein acting as amphoteric electrolytes and their physical behaviour will depend on the pH of the environment in which the molecules exist. This is indicated by Figure 30.2, showing a simplified protein molecule with just one acidic and one basic side group. 

Peptides and proteins are composed of a-amino acids linked by amide bonds (see Section 13.1). Their properties, for example the ability of enzymes to catalyse biochemical reactions, are dependent upon the degree of ionization of various acidic and basic side-chains at the relevant pH. This aspect will be discussed in more detail in Section 13.4, but, here, let us consider a simple amino acid dissolved in water at pH 7.0. An a-amino acid has an acidic carboxylic acid group and a basic amine group. Both of these entities need to be treated separately. 

Since proteins contain a lot of acidic and basic side chains acting as weak acids and bases, respectively, proteins are buffering substances, too. If you mix buffer solutions with protein solutions, pH may be altered because the concentration of protein s buffering residues may exceed the capacity of the (chemical) buffer. For instance, bovine serum albumin contains 59 basic (Lys) and 99 acidic (59 Asp plus 40 Glu) residues per mole a solution of 10 mg/ml (1%) BSA contains 9 mM basic and 14.5 mM acidic residues, and phosphate-buffered saline (PBS) contains only 10 mM phosphate. As a consequence of this example (a) the concentration of the chemical buffer should be high enough to act as a buffer, (b) choose a chemical buffer the pK of which is nearby the pH to be stabilized, and (c) adjust the pH after all components are mixed. 

This raises another question. Why is the serine hydroxyl an effective nucleophile when water and other hydroxylic compounds clearly are not similarly effective Apparently, the nucleophilicity of the serine —CH2OH is enhanced by acid-base catalysis involving proton transfers between acidic and basic side-chain functions in the vicinity of the active site. The serine is believed to transfer its OH proton to an amphoteric10 site B—A—H on the enzyme at the same instant that the proton of B—A—H is transferred to another base B e (Equation 25-8). These proton transfers are, of course, reversible ... 

For our example, let us consider the arduous task of learning common amino acids not only by structure but also by both the three- and one-letter abbreviations. Furthermore, we want students to distinguish between acidic and basic side chains. Such a task is common in biochemistry either in introductory or upper-level course offerings. Frequently, the instructor will make the assignment to memorize the list and leave the students to do it (or not). Based on Herron s principle of minimum effort (Herron 1996), students will need to recognize the value of the learning goal to devote effort toward it. On the one hand,... 

In globular proteins, the folding of the polypeptide chain is such that the amino acids with nonpolar side chains are assembled in the interior to form a hydro-phobic core, whereas the amino acids with polar and charged side chains tend to be at the surface to interact with the (aqueous) solvent. This oil-drop-like distribution of hydrophilic and hydrophobic amino acids is of importance for the functionality and stability of a protein because pK values of acidic and basic side chains can be shifted in nonpolar environment by several units, and internal hydrogen bonds are strengthened because the donors and acceptors do not have to compete with water molecules [133, 134J. 

Some amino acids, such as aspartic acid and lysine, have acidic or basic side chains. These additional ionizable groups complicate somewhat the acid—base behavior of these amino acids. Table 28.1 lists the pAT values for these acidic and basic side chains as well. 

While all proteins contain the peptide backbone, each protein has its own characteristic sequence of side chains, which gives it its characteristic properties. Different proteins have different proportions of acidic and basic side chains, and hence have different isoelectric points, in a solution of a particular hydrogen ion concentration, some proteins move toward a cathode and others toward an anode depending upon the size of the charge as well as upon molecular size and shape, different proteins move at different speeds. This difference in behavior in an electric field is the basis of one method of separation and analysis of protein mixtures electrophoresis. 

FIGURE 38.26 Acidic and basic side chains on tricyclic skeletons. 

The alkyl side chains (R) can be divided into neutral, acidic and basic side chains. Those with alkyl or aryl side chains are neutral, those with amine (or related) side chains are basic, while those with carboxylic acid side chains are acidic. 

Animal glues are derived by the hydrolysis of the protein constituent collagen of animal hides and bones. Collagen in its natural state is water insoluble and must be conditioned to solubilize the protein. Collagen molecules are triple helices of amino acid sequences and contain both nonpolar and charged acidic and basic side chains. The conversion of... 

Changes in pH also affect acidic and basic side chains and those proteins in which they occur. Thus, all amino acids exist in solution in ionic forms, but the actual form (and charge) is determined by the solution pH. 

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