- Amino acids and proteins questions
- Central dogma of molecular biology
- Central dogma - revisited
- Peptide bonds: Formation and cleavage
- Special cases: Histidine, proline, glycine, cysteine
- Amino acid structure
- Isoelectric point and zwitterions
- Classification of amino acids
- Four levels of protein structure
- Conformational stability: Protein folding and denaturation
- The structure and function of globular proteins
Peptide bonds are formed when the amine group of one amino acid binds with the carbonyl carbon of another amino acid. We will learn more about peptide bonds and how the cleaving process occurs. By Tracy Kovach. Created by Tracy Kim Kovach.
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- Does acid hydrolysis of peptide bonds occur in the stomach?(32 votes)
- Not really. The peptidic bond is quite stable, so acid hydrolysis is very slow and requires high temperatures. Proteins are mostly degraded in the digestive tract by proteases(44 votes)
- When she says "cleave" she means they are cut off, correct?(21 votes)
- what is the nucleophilic addition elimination reaction?(8 votes)
- In this case it is when the nitrogen acts as a nucleophile and attacks the carobnyl carbon. This bonds the cabonyl carbon to the nitrogen and the electrons are pushed to the oxygen, this results in the double bond turning into a single bond and oxygen obtaining a negative charge. That is the "addition" portion. The hydroxyl group is protonated making it a good leaving group and the double bond reforms and pushes out the leaving group as water. That is the "elimination" portion.(14 votes)
- So I understand that acid hydrolysis is non-specific, as opposed to proteolysis that cleaves at certain sites. But, in acid hydrolysis, does it always split into single amino acids, or because of it's lack of specificity, do you generate a mixture of individual amino acids, as well as polypeptides of various lengths?(8 votes)
- I think once the reaction is complete, you would be left with individual amino acids. A strong acid completely disassociates during a reaction. Although, I would suppose that as the reaction occurred, you would get a mix of single amino acids and fragments of the original chain. Not sure how the reaction would happen with a weak acid, I would be interested to find out.(5 votes)
- 6:56"you probably don't need to memorize which proteases cleave after which amino acids..."
Um, trust me for the MCAT, you absolutely do. You also need to know about chymotrypsin which cleaves the carboxyl side of large hydrophilic amino acids like tyrosine, phenylalanine and tryptophan.(10 votes)
- Isn't histidine also basic? And thus trypsin would cleave on the C term of his as well (not just lys and arg)?(8 votes)
- Trypsin is a protease enzyme, so remember that enzymes have a preference for certain structures based on the active site. When proteins are cleaved by trypsin, only residues with Lysine or Arginine nearby the C terminus are cut.
Compare Histidine with it's beta imidazole group to Lysine's epsilon amino group and Arginine's delta guanidinium group. You can see how the physical geometry affects biology. Lysine and Arginine have some of the longest basic R groups of the amino acids.(3 votes)
- She says that the "R" represents the "side chain". However, I don't understand what a "side chain" is. Can someone please explain that to me?
Thank you!(2 votes)
- All the amino acids have a carbon atom bound to a hydrogen atom, an amino group, a carboxylic acid group and a "side chain". The side chain is the part of the molecule where amino acids differ. With the exception of glycine and proline, the "side chain" is a chain of carbons that sticks out of the side of a polypeptide chain.
In the case of glycine, it is a hydrogen atom; in the case of alanine is a CH3 group; in the case of threonine, it is a CHOH - CH3 group, and so on.(10 votes)
- Can changing the PH of a solution containing two amino acids increase the likelihood of their amino and carboxyl groups connecting forming a peptide?
For example say I have a solution containing Cysteine (isoelectric point of 5.02) and I want to have it combine with Lysine (isoelectric point of 9.59) to form a peptide. Would changing the PH improve the results?(4 votes)
- I assume the question is regarding improving the chances of alpha-amine forming the peptide bond instead of the side chain amine on Lys. When you are coupling cystein to lysine, you can expect to get a mixture of both kinds of peptide bonds, but adjusting the pH could yield, to some extent, better proportion of the desired type of peptide bond and you could attempt to separate the desired peptide from the mixture. However, in lab, this is normally achieved by use of protecting groups, such as Dde, which will mask the amine on the side chain of Lys (essentially making it non-reactive), but leaving the alpha amine free to couple with cys to form the desired peptide.(3 votes)
- Is acid catalysis the same as the acid hydrolysis that she is talking about?(2 votes)
- No. Acid catalysis is when an acid donates a proton in an intermediate step in a reaction (like the aldol condensation) so that it can run to completion. Acid hydrolysis is when an acid disrupts a bond and breaks it.(6 votes)
- When you draw out the peptide bond, you describe resonance delocalization. If I understand this correctly, you are saying the chain cannot rotate along the axis of the peptide bind because it will shift between these two formations in which the oxygen contains the double bond and then the nitrogen contains the double bond. This shift prevents rotation, is that correct?(3 votes)
- I expect this shift to prevent rotation because of the rigidity associated with double bonds and triple bonds. The double bond in the resonance will be between the carbon of the carboxyl and the nitrogen.(2 votes)
Let's talk about the peptide bond. Now, proteins are formed from the folding of polypeptide chains. And polypeptide chains are formed by linking amino acids together. And these links are called peptide bonds. So before we can work our way up to the fully-formed and functional protein, we have to start at the very beginning by forming a peptide bond between the first two amino acids. So let's review the structure of an amino acid really quickly. Here we have our backbone. We have our amino group, our carboxylic acid group. Here is our alpha carbon. And then, the r represents our side chain. Now, peptide bonds are formed by the nucleophilic addition-elimination reaction between the carboxyl group of one amino acid and the amino group of another amino acid. So let me show you what that looks like here. Let's have another amino acid drawn right here. So the electron pair on the amino group of the second amino acid comes over to form a bond with the carbonyl carbon of the first amino acid. You give off a water molecule in the process, and then you get your newly-formed dipeptide. And here is our newly-formed peptide bond. Now, remember that a peptide bond is just an amide bond that is formed between two amino acids. And you should also make note of the fact that this bond is a rigid and planar bond that is stabilized by resonance delocalization of this nitrogen's electrons to this carbonyl oxygen. So we can draw that out here. Remember that there is a lone pair of electrons on this nitrogen that can move here. And then, these electrons will move to this oxygen atom, which also has its own two lone pairs of electrons. So it can also be represented like this. And we'll have the formation of a double bond here and then an extra lone pair on the oxygen atom. So as you can see, the peptide bond with this resonance delocalization of electrons has a lot of double bond character. And because of this double-bond-like character, the peptide bond is a very rigid and planar one. But don't confuse this with thinking that an entire polypeptide chain would be a rigid-like structure because-- even though there isn't much rotation about the peptide bond-- you do still have for free rotation about these alpha carbon atoms here. So now, here we can see we have a dipeptide. And if we kept adding amino acids along in a chain here, we would have a polypeptide. Now, if we take a closer look at the backbone of this chain, we can see that there is a pattern formed by the atoms that form this backbone. And here, you have a nitrogen atom, the alpha carbon, and a carbonyl carbon. And then, it repeats with the nitrogen atom, the alpha carbon, and a carbonyl carbon. And you get a pattern that looks like this. And each time you add a new amino acid, the pattern just repeats. So that, whatever length of your polypeptide chain, you always start out with a nitrogen atom and you always end with the carbonyl carbon. And so this end of the backbone of the polypeptide chain is called the amino or N terminal. And then, this end of a polypeptide chain is called the C terminal. And then once, within a polypeptide chain, each amino acid is called a residue. So that's the formation of a peptide bond and a polypeptide chain. So now how do we go about breaking this peptide bond to get two amino acids again? Let's give ourselves just a little bit more room here to work, and we'll redraw a bond between two amino acids as a peptide bond here. And remember that here is our peptide bond-- just to highlight it for you. And we can break this peptide bond in a process called hydrolysis. So if we have hydrolysis of this peptide bond, then we go back to forming two free amino acids. The hydrolysis of a peptide bond is helped along by two common means, and those two means are with the help of strong acids or with proteolytic enzymes. So when we use strong acids, we call this acid hydrolysis. And acid hydrolysis, when combined with heat, is a nonspecific way of cleaving peptide bonds. So say you have a long polypeptide chain. And then, you throw this polypeptide into a pot with some strong acid, and then turn up the stove to add a little heat. Then, you would just end up with a jumbled up mix of amino acids as each of the peptide bonds gets cleaved. So the other way of cleaving a peptide bond is with proteolysis. And proteolysis is a specific cleavage of the peptide bond with the help of a special protein, an enzyme called a protease. So unlike acid hydrolysis, proteolytic cleavage is a specific process. And you can choose which peptide bonds you cleave because proteases are pretty picky about where they will cut, and many of them will only cleave peptide bonds between certain specific amino acids. One example of this is with the protease trypsin. Trypsin only cleaves on the carboxyl side of basic amino acids, like arginine and lysine. And interestingly, this is the same enzyme that is produced by our pancreas to help us digest food. So now say we have the following polypeptide chain-- and it can be any old, arbitrary polypeptide chain-- and say we add trypsin to the environment that this polypeptide chain is in. And here I'm just representing the amino acids as their abbreviated form. Now with the addition of trypsin, where would this polypeptide chain be cleaved? Well, remember that trypsin cleaves on the C terminus of arginine and lysine. Here we have an arginine, and this would be considered the C terminal of arginine, since it's closest to the C terminal of the polypeptide chain. So we would get cleavage here. And then, likewise, we would have cleavage on the C terminal of this lysine residue here. And so with this particular polypeptide chain, you would end up with three different fragments after the addition of trypsin since it cleaves in these very specific places. And there are many other examples of specific proteases that cleave in at certain parts of polypeptide chains. And you probably don't really need to memorize which proteases cleave after which amino acids, but you should probably remember that they are just specific means of breaking a peptide bond-- unlike acid hydrolysis over here, which is a very nonspecific way of cleaving a peptide bond.