I guess I don't understand amino acid pkas...

[MCAT guy]

So BR has a question that says, what does histidine do at pH 7? Migrate to anode/cathode/not migrate

well, I look at my pKa's and see 1 @ 2 / 2 @ 6 / 3 @ 9

So I think, well at 7 I would see both #1 and #2 deprotonated which puts me at a neutral state. No migration.

WRONG.

BR: The isoelectric point is 7.6 so you are positive, go to the cathode.

OK great, why do I have a pKa2 at 6 if it doesn't mean anything. A full point higher pH and we are still saying it is protonated?

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[Rayhaan]

The 2 pka values around the zwitterion determine the pI which is what you need to calculate in order to solve this question. Histidine is the only basic amino acid to have a sidechain pka below 7 (6ish like you said). Amino side chains are about 9-10.

6 + 9 = 15
15/2 = 7.5

Since pH is 7 we are not completly neutral. Which way does it go?
A pH of seven is not a full unit from 7.5 so there are likely some positives left. So it will go towards the cathode.

Your method could also work, but you forgot the fact that histidine side chain pH is not equal to 6, it is slightly above. So therefore, there would still be some NH3+ giving a slight net +.

 

[RogueUnicorn]

You have to consider the meaning of pKa properly. Let's look at the following scenarios:

1) pH=6
At this pH, half of the His have a +1 on the side chain, half have a 0. In the overall molecule, we'll have a +1 on the N-term, and -1 on the C-term, adding to zero. Thus, half the molecules have a +1 charge, and the other half is neutral. The NET charge in a bag of His then, is the average of the two, or +0.5 at pH=6.

2) pH=7
The N- and C-terms still cancel to 0, so let's look at the side chain. At pH 7, you have a 1:10 ration of + charge to neutral as given by H-H equation. That is to say, if you had a bag of them, the NET charge would be +0.1. Still positive.

 

[MCAT guy]

You have to consider the meaning of pKa properly. Let's look at the following scenarios:

1) pH=6
At this pH, half of the His have a +1 on the side chain, half have a 0. In the overall molecule, we'll have a +1 on the N-term, and -1 on the C-term, adding to zero. Thus, half the molecules have a +1 charge, and the other half is neutral. The NET charge in a bag of His then, is the average of the two, or +0.5 at pH=6.

2) pH=7
The N- and C-terms still cancel to 0, so let's look at the side chain. At pH 7, you have a 1:10 ration of + charge to neutral as given by H-H equation. That is to say, if you had a bag of them, the NET charge would be +0.1. Still positive.

Thanks to both of you.

This does make sense, for some reason I forgot that when pH = pKa that means there is an even amount of each, instead of me just thinking when the pH is higher, that means the thing is deprotonated (it does, but I forgot quantitatively how much). Thx

Theoretically though, since this is Ka and we are talking about ratios, the ratio is NEVER has zero of anything, so techinically there would always be positive charge, albeit so small to be negligible... so this become a point of saying 10:1 isn't enough to cancel it out, 100:1? 1000:1? 10000:1?

I guess you just need to know when there is too much ratio to cancel out the rest.

 

[Rayhaan]

Typically 10:1 would be the max. Remember for typical buffers this is also the max buffering capacity. 10:1 is equivalent to a 1 pH change, which is the max capacity of buffers. So yes, I would just assume that if the pH change was greater than 1 it would be able to cancel out most surplus charge.