ABSTRACT
Histidine and tryptophan (Figure 4.1) are both aromatic heterocyclic amino acids that are considered to be electron-rich amino acids susceptible to oxidation.1,2 Histidine contains the imidazole ring and tryptophan contains the indole ring. However, histidine is a polar amino acid, while tryptophan is a nonpolar amino acid. The majority of the reactions of histidine involve substitution of one or both of the ring nitrogens (while the nitrogens are equivalent in imidazole, they differ somewhat in reactivity in histidyl residues in proteins both from structure and electrostatic environment), while the majority of tryptophan modications occur at the second carbon on the indole ring. This difference likely reects the difference in the nucleophilicity of the imidazole nitrogens and the indole nitrogen; the pKa for the nitrogen on the imidazole ring of histidine is approximately 6.8, while that for the pyrrole nitrogen in tryptophan is 17, which, as noted by Jack Kyte,3 is greater than that for water (15.8).
