Lecture 4: Amino Acid Properties

Case Study

• patient with type 1 diabetes present to the ER with blood ph of 7.1, which is a sign of metabolic acidosis

• Recall Bohr effect in which a decrease of pH reduces hemoglobin’s affinity for O2

• Examination reveals the histidine residue becoming protonated and forming a salt bridge, resulting in the release, instead of affinity for O2

• How can a minor change in a AA sequence change the function of an entire protein

Are all molecules zwitterions at psychological pH

Why does the

Titration of histidine

• how many function groups can be protonated and deprotonated

• Therefore how many buffering regions and exists at what pH?

• three functional groups

• Three buffering regions around the three pKas

The Bohr effect

• what happens to histidine at physiological pH

  • What happens

  • What does his forms what with what amino acid functional group

  • What is histine’s new function?

• physiological pH, histidine side chains are mostly deprotonated

• Therefore, under acidic conditions, there is an increase in H+ concentration which protonated His 146

• His will forms a salt bridge with Asp 94, changing the non-covalent interactions in the protein to stabilize the molecule and therefore release O2