Written by Merel Dagher (PEACE Advisor)

Histidine, one of the polar, charged amino acids, has three ionizable groups. Match the correct overall charge of histidine to the pH. (pKa1=1.8, pKa2=6.04, pKa3=9.33)
a.     At pH 1, His has a net charge of +1.

b.     At pH 3, His has a net charge of +1.

c.     At pH 4, His has a net charge of +2.

d.     At pH 7, His has a net charge of -1.

e.     At pH 10, His has a net charge of -2.

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The correct answer is b. It’s important to remember how the pKa’s of the histidine groups and how they relate to pH. 
Given this, at a pH less than 1.82, all of His will be protonated, thus having an overall net charge of +2 (therefore, a is wrong). When you have a pH greater than 1.82 and less than 6, the carboxy group will be deprotonated, giving His an overall charge of +1 (making b correct and c incorrect). At pH greater than 6 and less than 9.17, His will have both the carboxy and side chain deprotonated, giving it an overall charge of 0 (making d incorrect). Finally at a pH above 9.17, His will be completely deprotonated, giving it an overall charge of -1 (making e incorrect).

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