At physiological pH buffering action in the blood is caused by

Maximal buffering capacity occurs at pH equal to pKa of the buffer. Therefore, to work as the best buffer at physiological pH amino acid should have pKa value close to physiological pH (7.4). Amino acids can have buffering action due to three ionizable groups:- α-carboxyl group:- Different amino acids have pKa value of α-carboxyl group between 3.5-4. So, the carboxyl group of amino acids has maximum buffering capacity between pH 3.5-4. α-amino group:- Different amino acids have pKa value of α-amino group between 8.0-9.0. Thus, the α-amino group has maximum buffering capacity between pH 8.0-9.0. Special ionizable group (in some amino acids):- Among the special ionizable group of amino acids, imidazole group of histidine has pKa value 6.5-7.4, which is closest to physiological pH. Hence, histidine (due to imidazole group) has maximum buffering capacity at physiological pH.