Glutamic acid ionization

The maximum acid-combining capacity of keratin fibers, from reaction with simple acids such as hydrochloric, phosphoric, or ethyl sulfuric acid, is approximately 0.75mmol/g for unaltered human hair and about 0.82mmol/g for wool fiber [104]. This value approximates the number of dibasic amino acid residues in the fibers [105] (i.e., the combined amounts of arginine, lysine, and histidine) see Table 5-15.The primary sites for interaction with acid (protons) are probably the carboxylate groups of aspartic and glutamic acids (ionized by interaction with the dibasic amino acid residues) and the dibasic amino acid groups themselves. 

Arnold, R. J. Reilly, J. P. Observation of tetrahydrofolyl-poly-glutamic acid in bacteria cells by matrix assisted laser desorption/ionization mass spectrometry. Anal. Biochem. 2000,281,45-54. 

The most significant amino acids for modification and conjugation purposes are the ones containing ionizable side chains aspartic acid, glutamic acid, lysine, arginine, cysteine, histidine, and tyrosine (Figure 1.6). In their unprotonated state, each of these side chains can be potent nucleophiles to engage in addition reactions (see the discussion on nucleophilicity below). 

In addition to the a-amino and a-carboxyl groups those amino acids with an extra ionizable group will also have a pvalue. Glutamic acid is an example of an amino acid with an extra acidic group (COOH) on the y-carbon, and lysine is an example of an amino acid with an extra amino group on the e-carbon atom. As a result they each have three ionizable groups and three pKa... 

Some amino acids have additional ionizable groups in their side-chains. These may be acidic or potentially acidic (aspartic acid, glutamic acid, tyrosine, cysteine), or basic (lysine, arginine, histidine). We use the term potentially acidic to describe the phenol and thiol groups of tyrosine and cysteine respectively under physiological conditions, these groups are unlikely to be ionized. It is relatively easy to calculate the amount of ionization at a particular pH, and to justify that latter statement. 

Similar calculations as above for the basic side-chain groups of arginine pK 12.48) and lysine pK 10.52), and the acidic side-chains of aspartic acid (pATa 3.65) and glutamic acid (pAfa 4.25) show essentially complete ionization at pH 7.0. However, for cysteine (pATa of the thiol group 10.29) and for tyrosine (pAfa of the phenol group 10.06) there will be negligible ionization at pH 7.0. 

When the R group contains another ionizable group, the amino acid will have more than two dissociation constants. The carboxylic acid gronps of aspartic acid and glutamic acid, the amine of lysine, and the guanidino group of arginine will all... 

The amino acids in question are the basic amino acids lysine, arginine, and histidine, and the acidic amino acids aspartic acid and glutamic acid. The side-chain functions of these amino acids, ionized at pH 7 (see Box 4.7), act as acids or bases. In a reverse sequence, protons may be acquired or donated to regenerate the conjugate acids and conjugate bases. 

It is easy to see that the glutamic acid side-chain, ionized at pH 7, can attract the positively charged acetylcholine by means of ionic interactions. This allows binding, and locates the ester function close to the serine side-chain and the imidazole ring G igure 13.4). 

The active site of the enzyme contains a glutamic acid residue that is ionized at pH 7 and supplies the base. A histidine residue, partially protonated at pH 7, in turn supplies the proton necessary to form the common enol (Figure 13.6). 

An additional point should be noted from table 3.3. Whereas the amino acid side chains (R groups) that are normally charged at physiological pH are restricted to five amino acids (aspartic acid, glutamic acid, lysine, arginine, and sometimes histidine), a number of potentially ionizable R groups are part of other amino acids. These include cysteine, serine, threonine, and tyrosine. The ionization reac-... 

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