# Isoelectric Point

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#### MedPR

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So the isoelectric point is the average of the pka values.

However, for something like Lysine, why is it pka2+pka3/2? Why don't you use pka1?

So the isoelectric point is the average of the pka values.

However, for something like Lysine, why is it pka2+pka3/2? Why don't you use pka1?

isoelectric point is when net charge is 0.

So lysine is a weak base. Lets go from fully protonated to fully deprotonated. (btw, this is TBR method that I liked a lot)

Fully protonated state has 2 protons with the nitrogens and one on the carboxylic acid. A net +2 charge due to the nitrogens. So pKa1 is losing the first proton, H3(2+) --> H2(+)

Now we lose the second proton. pKa2 is H2(+) --> (H). This! This is when there is no net charge. When pH = pKa2, then that is when the H2(+) = (H). So lets go a little higher till it's all (H). This is pKa2 + pKa3 / 2. This is the isoelectric point or one of the equivalence points in the titration graph.

Lose the last proton. pKa3 is no H and a net negative charge.

isoelectric point is when net charge is 0.

So lysine is a weak base. Lets go from fully protonated to fully deprotonated. (btw, this is TBR method that I liked a lot)

Fully protonated state has 2 protons with the nitrogens and one on the carboxylic acid. A net +2 charge due to the nitrogens. So pKa1 is losing the first proton, H3(2+) --> H2(+)

Now we lose the second proton. pKa2 is H2(+) --> (H). This! This is when there is no net charge. When pH = pKa2, then that is when the H2(+) = (H). So lets go a little higher till it's all (H). This is pKa2 + pKa3 / 2. This is the isoelectric point or one of the equivalence points in the titration graph.

Lose the last proton. pKa3 is no H and a net negative charge.

So this method requires you to know the side chains?

Edit: I just read the method and I guess it is pretty simple. I'm not understanding this part though

The pI is found by summing the number of basic amino acids plus one, and taking th epka with that numerical subscript and averaging it with the next pka value sequentially up. So if a protein has two lysines, one arginine, and three histidines, then the pI is an average of pka7 and pka8.

Isn't this only true if both the carboxyl end and the amine end of the protein are protonated? Can't there be a time when the amino end is protonated but the carboxyl end is not?

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kind of. you just have to memorize the basic amino acids as those are the only ones that you do pka2+3/2 with. others you just do 1+2 /2

seems like such a chore, memorizing amino acids...