pKA on UW

[acciddropping]

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UW question on pKA and I can hardly recall anything about pKA - "Lysine has pKA 2.2, 9.2 and 10.7 and asks the most likely net charge at physiologic pH"
Based on the explaination, that's how I understand it. Please let me know if it's correct.
Physiologic pH = 7.4
a) pKA 2.2 < pH ==> -1
b) pKA 9.2 > pH ==> +1
c) pKA 10.7>pH ==> +1
------------------------------
net charge = +1

However, I don't understand the rest of the explanation
* Lysine would have +2 charge if pH is less than 2.2, no charge between 9.2 and 10.7, -1 charge at pH greater than 10.7 and lysine could only have -2 charge at extremely high pH values.

Can you please explain how they get them in an easy way? Thanks so much in advance.

 

[alicealicealice]

Chemistry aside think about a pKa as a measure of how bad the moiety (group) wants a proton
Rule 1:
If the the pKa is GREATER than the pH, the moiety wins and gets the proton.
If the pKa is LESS than the pH, the moity loses and does not get the proton.
Rule 2:
A moiety with pKa < 7 is weak acid, they start off with a negative charge (acids are proton donors). Ex: R-COO(-)
A moiety with pKa > 7 is a weak base, they start off neutral (bases are proton acceptors). Ex: NH3

So now lets look at lysine @ physiological pH = 7.4 and play the game.
pKa 2.2 means its an R-COO(-) looking for a proton. But 2.2<7.4 so he loses and stays a negative charge--> (-1)
pKa 9.2 means its an NH3 looking for a proton. 9.2>7.4 so he wins and becomes and becomes NH4(+)-->(+1)
pKa 10.2 means its an NH3 looking for a proton. 10.2>7.4 so he wins and becomes and becomes NH4(+)-->(+1)
Net results = (-1) + (+1) + (+1) = +1

This has relevance for drug excretion. For example, aspirin is an acid right? its PkA is 3.5.
So it was want to trap acid in the urine, we want it in an ionized form (charged molecules cant cross phospholipid membranes), i.e we want it to keep that negative charge and not "win" a proton. So we alkalize the urine so pH>pKa.
Simple concept, but theres a mneumonic.
To get rid of Acid, keep the urine pH Above the pKa
To get rid of Base, keep the urine pH Below the pKa

Why are local anesthetics injected with HCO3-? Lidocaine is a weak base with a pH of ~8.0. It needs to be in a non ionized form to enter the cell (charged molecules cant cross phospholipid membranes). So by making the local pH higher than the pKa, lidocaine stays non ionized and enters the cell. Onces it hits the cellular pH of 7.4 it picks up a proton, is trapped in the cytoplasm, and is able to exert its effects on the Na channels.

 

[acciddropping]

Chemistry aside think about a pKa as a measure of how bad the moiety (group) wants a proton
Rule 1:
If the the pKa is GREATER than the pH, the moiety wins and gets the proton.
If the pKa is LESS than the pH, the moity loses and does not get the proton.
Rule 2:
A moiety with pKa < 7 is weak acid, they start off with a negative charge (acids are proton donors). Ex: R-COO(-)
A moiety with pKa > 7 is a weak base, they start off neutral (bases are proton acceptors). Ex: NH3

So now lets look at lysine @ physiological pH = 7.4 and play the game.
pKa 2.2 means its an R-COO(-) looking for a proton. But 2.2<7.4 so he loses and stays a negative charge--> (-1)
pKa 9.2 means its an NH3 looking for a proton. 9.2>7.4 so he wins and becomes and becomes NH4(+)-->(+1)
pKa 10.2 means its an NH3 looking for a proton. 10.2>7.4 so he wins and becomes and becomes NH4(+)-->(+1)
Net results = (-1) + (+1) + (+1) = +1

This has relevance for drug excretion. For example, aspirin is an acid right? its PkA is 3.5.
So it was want to trap acid in the urine, we want it in an ionized form (charged molecules cant cross phospholipid membranes), i.e we want it to keep that negative charge and not "win" a proton. So we alkalize the urine so pH>pKa.
Simple concept, but theres a mneumonic.
To get rid of Acid, keep the urine pH Above the pKa
To get rid of Base, keep the urine pH Below the pKa

Why are local anesthetics injected with HCO3-? Lidocaine is a weak base with a pH of ~8.0. It needs to be in a non ionized form to enter the cell (charged molecules cant cross phospholipid membranes). So by making the local pH higher than the pKa, lidocaine stays non ionized and enters the cell. Onces it hits the cellular pH of 7.4 it picks up a proton, is trapped in the cytoplasm, and is able to exert its effects on the Na channels.

Wow! Thanks so much!! I understand them now. I love the way you explained especially the clinical relevance. Based on your explanation, here are some I tried out of the answer choices.

If it's @ pH = 2
pKa 2.2 means its an R-COO(-) looking for a proton. 2.2> 2 so he wins and become COOH --> (0)
pKa 9.2 means its an NH3 looking for a proton. 9.2>2 so he wins and becomes and becomes NH4(+)-->(+1)
pKa 10.2 means its an NH3 looking for a proton. 10.2>2 so he wins and becomes and becomes NH4(+)-->(+1)
Net results = (0) + (+1) + (+1) = +2

If it's @ pH = 10
pKa 2.2 means its an R-COO(-) looking for a proton. 2.2 < 10 but he loses and stays COO- --> (-1)
pKa 9.2 means its an NH3 looking for a proton. 9.2<10 but he loses and stays NH3 -->(0)
pKa 10.2 means its an NH3 looking for a proton. 10.2>10 so he wins and becomes and becomes NH4(+)-->(+1)
Net results = (-1) + (0) + (+1) = 0

 

[aspiringmd1015]

do questions like this come often?