Histidine Amino Acid, Acidic or Basic?

[leathersofa]

Is the amino acid histidine an acidic or basic amino acid? TBR lists it as one of seven common triprotic acids with pKa = 6.05 along with arginine (pKa = 13.21) and lysine (pKa = 10.80)

However, on the Internet, histidine, arginine and lysine are listed as basic amino acids.
http://www.sigmaaldrich.com/life-sc...arning-center/amino-acid-reference-chart.html

Can someone help me out with this? How do we determine whether amino acids are basic or acidic or am I missing something here?
Thank you

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[eudovcic]

If TBR lists arginine as pKa=13.21, would that not mean the Ka for arginine is relatively low thus its acidity is low as well?

Or is it referring to the relative acidity of the H+'s and not the amino acid itself?

 

[leathersofa]

It lists the pKa values for common side chains

So would that mean the H+'s or the amino acid?
For a page reference, the table is on page 279 of TBR General Chem Part 1

 

[monkeyvokes]

Is the amino acid histidine an acidic or basic amino acid? TBR lists it as one of seven common triprotic acids with pKa = 6.05 along with arginine (pKa = 13.21) and lysine (pKa = 10.80)

However, on the Internet, histidine, arginine and lysine are listed as basic amino acids.
http://www.sigmaaldrich.com/life-sc...arning-center/amino-acid-reference-chart.html

Can someone help me out with this? How do we determine whether amino acids are basic or acidic or am I missing something here?
Thank you

basic: lysine, arginine, and histidine. The pkas of these are much higher than those of the acidic amino acids

acidic: aspartic acid (aspartate) and glutamic acid (glutamate) <-- these two are similar and have very acidic carboxylic acid side chains. take a look at their structure.

these amino acids are triprotic because they have three protons than can dissociate into solution. two on the main chain (amine and carboxy groups) and one on their unique side chains.
I am confused by your use the word "however," as both of your sources are in agreement.

If TBR lists arginine as pKa=13.21, would that not mean the Ka for arginine is relatively low thus its acidity is low as well?

Or is it referring to the relative acidity of the H+'s and not the amino acid itself?

yes the Ka for arg is low, it is a basic amino acid and requires a very high pH to dissociate its side chain's proton. lysine arg and his have low Kas and high pKas. The pKa you have is for the side chain, not the main chain. The main chain amino and carboxy groups have relatively similar pKas in all of the amino acids.

 

[leathersofa]

basic: lysine, arginine, and histidine. The pkas of these are much higher than those of the acidic amino acids

acidic: aspartic acid (aspartate) and glutamic acid (glutamate) <-- these two are similar and have very acidic carboxylic acid side chains. take a look at their structure.

these amino acids are triprotic because they have three protons than can dissociate into solution. two on the main chain (amine and carboxy groups) and one on their unique side chains.
I am confused by your use the word "however," as both of your sources are in agreement.

Okay, so I am still a bit confused about basic vs acidic amino acids. For instance, the pKa of HIO = 10.70, but HIO is still considered an acid. We do not consider it a "basic" acid.
However, for the amino acid lysine (pKa = 10.8), it is not considered an acidic amino acid. Rather, it is considered a "basic" amino acid though its pKa is similar to hypoiodous acid. Why so?

Also, when you say there are two protons on the main chain..is the first proton from NH2 and the second proton from COOH?
thank you!

 

[FeinMS]

Okay, so I am still a bit confused about basic vs acidic amino acids. For instance, the pKa of HIO = 10.70, but HIO is still considered an acid. We do not consider it a "basic" acid.
However, for the amino acid lysine (pKa = 10.8), it is not considered an acidic amino acid. Rather, it is considered a "basic" amino acid though its pKa is similar to hypoiodous acid. Why so?

Also, when you say there are two protons on the main chain..is the first proton from NH2 and the second proton from COOH?
thank you!

I believe it has to do with the different reaction conditions in general chemistry and biochemistry. We call lysine a basic amino acid because at physiological pH, it tends to be protonated. We call HIO an acid because we're not dealing with physiological pH anymore. I believe it has something to do with arbitrary choice of reference.

Triprotic amino acids have 3 protons, one COOH, one alpha-NH3+, another at side chain

 

[monkeyvokes]

I believe it has to do with the different reaction conditions in general chemistry and biochemistry. We call lysine a basic amino acid because at physiological pH, it tends to be protonated. We call HIO an acid because we're not dealing with physiological pH anymore. I believe it has something to do with arbitrary choice of reference.

Triprotic amino acids have 3 protons, one COOH, one alpha-NH3+, another at side chain

yes you're exactly right. Biochemistry is typically done with the assumption that you're at the physiological pH of 7.4

and yes the two main chain protons are from the amino and carboxy group, check out the structures of amino acids.

 

[leathersofa]

I believe it has to do with the different reaction conditions in general chemistry and biochemistry. We call lysine a basic amino acid because at physiological pH, it tends to be protonated. We call HIO an acid because we're not dealing with physiological pH anymore. I believe it has something to do with arbitrary choice of reference.

Triprotic amino acids have 3 protons, one COOH, one alpha-NH3+, another at side chain

Okay, so histidine also is a basic amino acid but it's pKa is 6.50, which is less than the physiological pH so it tends to be deprotonated. Why is it still a basic amino acid then?

Regarding the triprotic amino acids, isn't the amine group NH2? because i looked up the structure of the basic amino acids on google images (link below) and it's NH2..so then if the NH2 donated a proton, would it become NH-...or is it actually NH3+ as you said?
http://www.biologie.uni-hamburg.de/b-online/ge16/27f.gif

Thank you so much, you are a saint!!

 

[eudovcic]

Okay, so histidine also is a basic amino acid but it's pKa is 6.50, which is less than the physiological pH so it tends to be deprotonated. Why is it still a basic amino acid then?

/QUOTE]

pKa does not necessarily equal pH.

pH = pKa + log([A-]/[HA])

So when pKa=6.5 it doesn't mean pH=6.5 unless you have equal concentration of acid and conjugate base.

 

[FeinMS]

Okay, so histidine also is a basic amino acid but it's pKa is 6.50, which is less than the physiological pH so it tends to be deprotonated. Why is it still a basic amino acid then?

Regarding the triprotic amino acids, isn't the amine group NH2? because i looked up the structure of the basic amino acids on google images (link below) and it's NH2..so then if the NH2 donated a proton, would it become NH-...or is it actually NH3+ as you said?
http://www.biologie.uni-hamburg.de/b-online/ge16/27f.gif

Thank you so much, you are a saint!!

Honestly, I think histidine is a b*tch. It confuses almost everyone in biochemistry learning about amino acids. Idk why it's called a basic amino acid, but since it's pKa is relatively close to the physiological pH, histidine is important in acid/base catalysis. Small change in pH can change the protonation state of the side chain unlike other acidic/basic amino acids.

Regarding the protonation state of carboxyl and amino group, at physiological pH, they exist as COO- and NH3+. I just said COOH and NH3+ to show which proton will be eliminated because you can't take a proton off NH2.

 

[enervate]

Okay, so histidine also is a basic amino acid but it's pKa is 6.50, which is less than the physiological pH so it tends to be deprotonated. Why is it still a basic amino acid then?

Histidine, like the rest of the potentially protonated/deprotonated amino acids is both acidic and basic. Whether it acts as an acid or a base depends on pH as others have so already so kindly pointed out. Classifying it either as strictly an acid or strictly a base is erroneous. In conditions where pH > pK_a, it is acidic. In conditions where pH < pK_a, it is basic.

Imagine if the His sidechain pK_a was equal to physiological pH. According to the Henderson-Hasselbach equation, there would be an equivalent amount of protonated and unprotonated His residues. This is, for our purposes, ideal for catalysis because, as you know, for enzymes complete a catalytic cycle, they must return to their original state. When an enzyme employs acid-base catalysis with a His residue, that residue must first act as a base and then as an acid or vice versa. If the pH were much higher than the pK_a, that His residue would readily act as an acid to donate a proton but it would be significantly longer before it could act as a base to receive a proton and return to its original state. This would be a relatively poor catalytic strategy. However, where the pH and pK_a are not much different, the residue readily acts as both an acid and a base to complete the catalytic cycle.

Considering the Henderson-Hasselbach equation and assuming the His sidechain pK_a is 6.8, at a physiological pH of 7.4, the ratio of [His-H]/[His] is 1/4. Compare with the Asp sidechain pK_a of 4.4: the ratio of [Asp-H]/[Asp] is 1/1000. The likelihood that an Asp residue is protonated under physiological pH is significantly lower than the likelihood that a His residue is protonated under the same pH. Therefore, the Asp residue can't be reliably used as an acid-base catalyst at physiological pH-- the enzyme wouldn't turn over fast enough to proceed with the next catalytic cycle.

 

[leathersofa]

Thank you so much!! That really cleared my confusion, thank you very very much

 

[rorsara]

Histidine never stops to confuse me.. Can anyone please help me answering this question?

what is the correct answer?

Under most biological conditions, however, histidine is considered to be a triprotic acid. This is due to the pKa of the _________ .

A. Other nitrogen in the imidazole ring, that possesses a hydrogen but no charge being much lower than the pH values normally found in a cell.

B. Other nitrogen in the imidazole ring, that possesses a hydrogen but no charge being much higher than the pH values normally found in a cell.

C. Carboxylic acid being much higher than the pH values normally found in a cell.

 

[BerkReviewTeach]

Is the amino acid histidine an acidic or basic amino acid? TBR lists it as one of seven common triprotic acids with pKa = 6.05 along with arginine (pKa = 13.21) and lysine (pKa = 10.80)

However, on the Internet, histidine, arginine and lysine are listed as basic amino acids.
http://www.sigmaaldrich.com/life-sc...arning-center/amino-acid-reference-chart.html

Can someone help me out with this? How do we determine whether amino acids are basic or acidic or am I missing something here?
Thank you

There are two different adjectives describing histidine here, "triprotic" and "basic".

First, there are seven triprotic amino acids, which means that seven can lose three protons during complete base-titration starting from their fully protonated states. They can be written as either H3A+ or H3A2+. Three of these seven are basic amino acids "His Lys Arg basic" and two of the seven are acidic (Glu and Asp).

By biochemistry convention, an amino acid is classified as basic if from its neutral state (uncharged or a zwitterion) it gains a proton. Lys, Arg, and His all pick up a proton from their neutral state and become cationic. Although we call them basic amino acids, they naturally occur in their conjugate acid form (Histidine because of its pKa being close to physiological pH can fluctuate between conjugate acid and neutral).

By biochemistry convention, an amino acid is classified as acidic if from its neutral state (uncharged or a zwitterion) it loses a proton. Flu and Asp gain a proton from their neutral state and become anionic. Although we call them acidic amino acids, they naturally occur in their conjugate base form (glutamate and aspartate at pH =7).