If you look at the structure of the “basic” amino acids (Arg, Lys, or His) in its charged version, you’ll see it has an -NH₃⁺. The “extra” H is already there. How can something be a base if it doesn’t have room to take on a proton? It can’t - is *was* a base, acted like one, and gave us the positive form which we call the conjugate acid. Because it “wanted” to act as a base, it did and now it’s an acid. So it can’t act as a base again until it gives up a proton.
On the opposite side of the coin, if you look at the structure of the “acidic” amino acids (Glutamatic acid (Glu) or Aspartic acid (Asp)) in its charged version (Glutamate or Aspartate, respectively), you’ll see it has a COO⁻. Where’s the H? It’s already gone! How can something be an acid if it doesn’t have a proton to give? It can’t - is *was* an acid, acted like one, and gave us the negative form which we call the conjugate base. Because it wanted to act as an acid it did and now it’s a base. So it can’t act as an acid again until it picks up another proton it can give up. Sound oppositely familiar?
When we say an amino acid is “acidic” or “basic, we mean in its NEUTRAL form it acts as an acid or a base. The “acidic” amino acids (Glu & Asp) have a neutral form that gives up a proton (acts as an acid), leaving that amino acid negative. And the “basic” amino acids (Lys, Arg, & His) have a neutral form that accept a proton, making it positively charged.
So the charged versions we see are the “conjugate” versions. And which version’s actually present at any given time depends on the pH (flipping power) and the coin weighted-ness (pKa). For the basic amino acids, these side chain pKas are: His: ~6.0; lysine: ~10.5; Arg: ~12.5
Physiological (bodily) pH (outside of special compartments) is ~7.4, which is well below the pKa for lysine and Arginine. Lower pH means more protons around, and Lys & Arg’s relatively high skas mean that they really want them, so Lys & Arg are usually positively-charged. Especially arginine. Histidine has a lower pKa which is closer to bodily pH so it exists in neutral and positively-charged forms and can go back and forth between them in order to facilitate reactions bit.ly/histidineimac
Arg has several things in common with the amino acid we looked at yesterday, Histidine (His, His). BOTH have “extra” nitrogen atoms in their side chains. Thanks to those N’s ability to use their lone pairs of electrons to snatch up “extra” protons, BOTH can be ➕ charged. And BOTH are able to better handle that charge by delocalizing among multiple atoms, becoming stabilized by RESONANCE. BUT, unlike that of His, Arg’s resonance is NOT in a ring (that is, Arg is NOT aromatic), and it doesn't have the aromatic system draining electrons and weakening the bond to H. Instead, Arg’s resonance occurs in a GUANIDIUM group (three N/H groups connected to a central C) attached 2 the backbone through a 3-carbon linker.
This R group might remind you of a detergent molecule. With a polar end (where atoms share their shared electrons unevenly leading to partly charged parts) to a nonpolar chain (where atoms share their electrons fairly and there’s even neutrality everyday, so it has nothing to offer water in the way of charged parts to be attracted to), both are AMPHIPHILIC (have both hydrophilic (the polar part) & hydrophobic regions (the nonpolar part)). Arg’s hydrophilic side usually dominates, so Arg’s usually found on surface of proteins, but it can also be found w/the linker buried & the charged end sticking out. This might remind you of our discussion of lysine bit.ly/lysineanalysis
Lysine looks a lot like Arg - it can even be positively-charged too, but it only has a single extra amino group and, unlike Arg, Lys’s charge is NOT stabilized by resonance. As a result, it’s more willing to give up H⁺ (act as acid), as evident in its lower pKa. That leaves Lys’ N with a lone pair of electrons & makes Lys a good BASE & NUCLEOPHILE (something that seeks out positively-charged atoms to bond to), so it can participate in cool reactions. more on basicity vs nucleophilicity here: bit.ly/nucleophilefiles
What bout Arg? Arg is usually found maximally protonated (and ➕). So it has lots of H’s. It *could* act as an acid & give one up, BUT that charge delocalization makes charged Arg very happy & stable. So it’s a MUCH weaker acid than His (and thus a stronger base). Therefore, unlike His, which exists as a mix of protonated (and ➕) & deprotonated (and neutral) forms at biological pH, Arg won’t give up a H⁺ unless solutions are VERY basic (i.e. high pH, meaning low H⁺). As a result, R is reliably ➕ & well-suited to interact with ➖ molecules, such as the phosphate groups studding nucleic acid backbones, making it great for protein-DNA interactions.
Its breakdown (catabolism) products are also really important. It serves a key role in the urea cycle which helps get rid of extra nitrogen (when you break down amino acids, even the ones with nitrogen only in the backbone, you have to get rid of the nitrogen responsibly, and the urea cycle provides a way to pass it off from molecule to molecule and release it as urea in your pee instead of the more toxic ammonia). The urea cycle, depending on where you enter, requires a lot of pass-offs and arginine is the “last step” - an enzyme called arginase helps it break that nitrogen off a urea (this also leaves you with a molecule of ornithine, which can continue picking up nitrogen and cycling on and one).
Another breakdown product of arginine is nitric oxide (NO), which serves as a signaling molecule & VASODILATOR (something which makes blood vessels expand to lower blood pressure). You get this product if NITROGEN OXIDE SYNTHASE (NOS) converts Arg into citrulline(which can do things like serve in the urea cycle or be used to make more Arg) & nitric oxide. The reaction involves 2 “monoxygenase” steps - first it converts arginine to N-hydroxyarginine (NOHA) & then it cleaves that to NO & citrulline. The reaction requires NADPH & oxygen.
Arginine is considered “conditionally essential.” Healthy adults can make their own (like by recycling that citrulline with the help of argininosuccinate synthetase & argininosuccinate lyase), but doing so is energetically costly. Preterm babies & rapidly growing people can’t keep up with demand and thus need to get it from food.
Arg was discovered in 1886 by Schulze & Steiger from lupine seedlings, with the name coming from the Greek word for silvery-white because of the color of the crystals he isolated. how does it measure up? systematic name: 2-Amino-5-guanidinopentanoic acid coded for by: CGU, CGC, CGA, CGG, AGA, and AGG chemical formula: C₆H₁₄N₄O₂ molar mass: 174.204 g·mol⁻¹ link to arginine resonance diagram: MEDCH400_PKA.pdf, Acids and Bases Reference: P. Bruice, Organic Chemistry, 6th Edition, Chapters 1.16-1.26, 7.9, 16.5. courses.washington.edu/medch562/pdf/MEDCH400_PKA.pdf
more about all sorts of things: #365DaysOfScience All (with topics listed) 👉 bit.ly/2OllAB0 or search blog: thebumblingbiochemist.com
If histidine is at a ph of 6 and is equally protonated and deprotonated would the net charge be +1 or 0 . Ive stated that my polypeptide has two histidines so therefore one of them has a 1+ net charge and another has a 0 or would it be better to say they both have a 0.5 net charge contributing to an overall pp charge of +1 at ph 6?
Your channel is surreal! Let's see how fast I grow up to the task of binge crunching through all the stuff you're uploading... I always thought of pH as a property that is apparently actually defined by the pKa and not pH. 🥸 Lots to learn. Thank you!
If you look at the structure of the “basic” amino acids (Arg, Lys, or His) in its charged version, you’ll see it has an -NH₃⁺. The “extra” H is already there. How can something be a base if it doesn’t have room to take on a proton? It can’t - is *was* a base, acted like one, and gave us the positive form which we call the conjugate acid. Because it “wanted” to act as a base, it did and now it’s an acid. So it can’t act as a base again until it gives up a proton.
On the opposite side of the coin, if you look at the structure of the “acidic” amino acids (Glutamatic acid (Glu) or Aspartic acid (Asp)) in its charged version (Glutamate or Aspartate, respectively), you’ll see it has a COO⁻. Where’s the H? It’s already gone! How can something be an acid if it doesn’t have a proton to give? It can’t - is *was* an acid, acted like one, and gave us the negative form which we call the conjugate base. Because it wanted to act as an acid it did and now it’s a base. So it can’t act as an acid again until it picks up another proton it can give up. Sound oppositely familiar?
When we say an amino acid is “acidic” or “basic, we mean in its NEUTRAL form it acts as an acid or a base. The “acidic” amino acids (Glu & Asp) have a neutral form that gives up a proton (acts as an acid), leaving that amino acid negative. And the “basic” amino acids (Lys, Arg, & His) have a neutral form that accept a proton, making it positively charged.
So the charged versions we see are the “conjugate” versions. And which version’s actually present at any given time depends on the pH (flipping power) and the coin weighted-ness (pKa). For the basic amino acids, these side chain pKas are: His: ~6.0; lysine: ~10.5; Arg: ~12.5
Physiological (bodily) pH (outside of special compartments) is ~7.4, which is well below the pKa for lysine and Arginine. Lower pH means more protons around, and Lys & Arg’s relatively high skas mean that they really want them, so Lys & Arg are usually positively-charged. Especially arginine. Histidine has a lower pKa which is closer to bodily pH so it exists in neutral and positively-charged forms and can go back and forth between them in order to facilitate reactions bit.ly/histidineimac
Arg has several things in common with the amino acid we looked at yesterday, Histidine (His, His). BOTH have “extra” nitrogen atoms in their side chains. Thanks to those N’s ability to use their lone pairs of electrons to snatch up “extra” protons, BOTH can be ➕ charged. And BOTH are able to better handle that charge by delocalizing among multiple atoms, becoming stabilized by RESONANCE. BUT, unlike that of His, Arg’s resonance is NOT in a ring (that is, Arg is NOT aromatic), and it doesn't have the aromatic system draining electrons and weakening the bond to H. Instead, Arg’s resonance occurs in a GUANIDIUM group (three N/H groups connected to a central C) attached 2 the backbone through a 3-carbon linker.
This R group might remind you of a detergent molecule. With a polar end (where atoms share their shared electrons unevenly leading to partly charged parts) to a nonpolar chain (where atoms share their electrons fairly and there’s even neutrality everyday, so it has nothing to offer water in the way of charged parts to be attracted to), both are AMPHIPHILIC (have both hydrophilic (the polar part) & hydrophobic regions (the nonpolar part)). Arg’s hydrophilic side usually dominates, so Arg’s usually found on surface of proteins, but it can also be found w/the linker buried & the charged end sticking out. This might remind you of our discussion of lysine bit.ly/lysineanalysis
Lysine looks a lot like Arg - it can even be positively-charged too, but it only has a single extra amino group and, unlike Arg, Lys’s charge is NOT stabilized by resonance. As a result, it’s more willing to give up H⁺ (act as acid), as evident in its lower pKa. That leaves Lys’ N with a lone pair of electrons & makes Lys a good BASE & NUCLEOPHILE (something that seeks out positively-charged atoms to bond to), so it can participate in cool reactions. more on basicity vs nucleophilicity here: bit.ly/nucleophilefiles
What bout Arg? Arg is usually found maximally protonated (and ➕). So it has lots of H’s. It *could* act as an acid & give one up, BUT that charge delocalization makes charged Arg very happy & stable. So it’s a MUCH weaker acid than His (and thus a stronger base). Therefore, unlike His, which exists as a mix of protonated (and ➕) & deprotonated (and neutral) forms at biological pH, Arg won’t give up a H⁺ unless solutions are VERY basic (i.e. high pH, meaning low H⁺). As a result, R is reliably ➕ & well-suited to interact with ➖ molecules, such as the phosphate groups studding nucleic acid backbones, making it great for protein-DNA interactions.
Its breakdown (catabolism) products are also really important. It serves a key role in the urea cycle which helps get rid of extra nitrogen (when you break down amino acids, even the ones with nitrogen only in the backbone, you have to get rid of the nitrogen responsibly, and the urea cycle provides a way to pass it off from molecule to molecule and release it as urea in your pee instead of the more toxic ammonia). The urea cycle, depending on where you enter, requires a lot of pass-offs and arginine is the “last step” - an enzyme called arginase helps it break that nitrogen off a urea (this also leaves you with a molecule of ornithine, which can continue picking up nitrogen and cycling on and one).
Another breakdown product of arginine is nitric oxide (NO), which serves as a signaling molecule & VASODILATOR (something which makes blood vessels expand to lower blood pressure). You get this product if NITROGEN OXIDE SYNTHASE (NOS) converts Arg into citrulline(which can do things like serve in the urea cycle or be used to make more Arg) & nitric oxide. The reaction involves 2 “monoxygenase” steps - first it converts arginine to N-hydroxyarginine (NOHA) & then it cleaves that to NO & citrulline. The reaction requires NADPH & oxygen.
Arginine is considered “conditionally essential.” Healthy adults can make their own (like by recycling that citrulline with the help of argininosuccinate synthetase & argininosuccinate lyase), but doing so is energetically costly. Preterm babies & rapidly growing people can’t keep up with demand and thus need to get it from food.
Arg was discovered in 1886 by Schulze & Steiger from lupine seedlings, with the name coming from the Greek word for silvery-white because of the color of the crystals he isolated.
how does it measure up?
systematic name: 2-Amino-5-guanidinopentanoic acid
coded for by: CGU, CGC, CGA, CGG, AGA, and AGG
chemical formula: C₆H₁₄N₄O₂
molar mass: 174.204 g·mol⁻¹
link to arginine resonance diagram: MEDCH400_PKA.pdf, Acids and Bases Reference: P. Bruice, Organic Chemistry, 6th Edition, Chapters 1.16-1.26, 7.9, 16.5. courses.washington.edu/medch562/pdf/MEDCH400_PKA.pdf
more about all sorts of things: #365DaysOfScience All (with topics listed) 👉 bit.ly/2OllAB0 or search blog: thebumblingbiochemist.com
This video was very useful, I watched it a few times and it has really improved my understanding. I can't thank you enough!
Glad it helped!
Very cool content. Thank you very much 🙏. As I understand: Arginine's R group is the most basic and vital for eg Nitric Oxide Synthase.
If histidine is at a ph of 6 and is equally protonated and deprotonated would the net charge be +1 or 0 . Ive stated that my polypeptide has two histidines so therefore one of them has a 1+ net charge and another has a 0 or would it be better to say they both have a 0.5 net charge contributing to an overall pp charge of +1 at ph 6?
Not sure sorry
So is arginine is the most basic amino acid?
Yep!
Your channel is surreal! Let's see how fast I grow up to the task of binge crunching through all the stuff you're uploading... I always thought of pH as a property that is apparently actually defined by the pKa and not pH. 🥸 Lots to learn. Thank you!
Thanks so much! Happy I can help