Question

Histamine has three ignitable groups with pK_a values of 1.8, 6.0 and 9.2. which pK_a, corresponds to the histamine side chain? in a solution at pH = 5.4, what percentage of the histamine side chains will carry a positive charge? what is the uniquely important acid-base characteristic of the histamine R group?

Answer 1

a) The histidine imidazole side chain plays a critical role in protein function and stability. Its importance for catalysis is underscored by the fact that histidines are localized to active sites in ∼50% of all enzymes. Further, the pKa values explain the pH-dependent stability differences between native and intermediate states over the pH range 5.5–6.5 and they suggest that imidazole deprotonation is not a barrier to the folding of this protein.

The conjugate acid (protonated form) of the imidazole side chain in histidine has a pK_a of approximately 6.0. This means that, at physiologically relevant pH values, relatively small shifts in pH will change its average charge. Below a pH of 6, the imidazole ring is mostly protonated as described by the Henderson–Hasselbalch equation.

b) pH = pKa + log

pKa - pH = log

antilog (pKa - pH) = antilog (6.0 - 5.4) = 4 = [acid]/[conjugate base],

or 4[conjugate base] = [acid]

Therefore, at pH 5.4, 4/5 (80%) of the histidine will be in the protonated form.

c)  Only the imidazole ring of the histidine R group has a pKa near physiological pH (pKa = 6.0), which suggests that histidine may provide buffering power in intercellular and intracellular fluids.