pH, pI and pKa

[MarinaD]

While doing UWorld practice, I saw a question that said that a high pI is normally associated with positive charges, and a low pI is associated with negative charges.

The explanation was: if the net charge is (+) at physiological pH, it has a high pI and needs a high pH to deprotonate all of the positively charged side chains.

I never fully understood pI, could someone please explain the above statement as well as a general breakdown on how to understand pH, pI and pKa when asked any of those as an MCAT question?

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[BerkReviewTeach]

The pI of an amino acid or protein is the pH at which it carries no net charge. So if you have a compound that carries a positive charge, then in order to make it neutral you need to deprotonate it. This is done by adding base, which causes the solution pH to increase. Eventually, after enough base has been added, the compound will be deprotonated and become neutral, meaning it has reached its pI. So the pI is higher than the original pH of the solution. Conversely, if you have a compound that carries a negative charge, then in order to make it neutral you need to protonate it. This is done by adding acid, which causes the solution pH to decrease. Eventually, after enough acid has been added, the compound will be protonated and become neutral, meaning it has reached its pI. So the pI is lower than the original pH of the solution.

The important thing to note with this topic is that there really are only five amino acids that have an impact on the pI: Lys, Arg, His, Asp, and Glu. These five can carry charges on their sidechains at pHs close to physiological pH. For Asp and Glu, the sidechain is a carboxylic acid, which goes from neutral to anionic when deprotonated. They typically lower the pI (making the pH necessary for the neutral species to exist lower.) For Lys, Arg, and His, the sidechain is a nitrogen-containing base, which goes from neutral to cationic when protonated. They typically raise the pI (making the pH necessary for the neutral species to exist higher.)

I hope this helps. There are a few really helpful tricks for determining pI and protein charge that you should master for your MCAT.

 

[MarinaD]

THANK YOU for this! Just to reiterate, pI is basically the "new pH" after we have tried to neutralize the charge on our amino acid. The comparison between pI and pH is just referring to the original pH of the solution and the new pH of the solution (pI). I might've simplified that a bit much but is that the correct understanding?

 

[BobbyKoch]

if BerkleyReviewTeach says it's right I certainly won't argue.

 

[BerkReviewTeach]

THANK YOU for this! Just to reiterate, pI is basically the "new pH" after we have tried to neutralize the charge on our amino acid. The comparison between pI and pH is just referring to the original pH of the solution and the new pH of the solution (pI). I might've simplified that a bit much but is that the correct understanding?

Exactly!