Amino acids are the building blocks of polypeptide chains which fold into 3D protein structures. Proteins are biopolymers that play critical structural and metabolic roles in living organisms, forming components of cell membranes, muscle fibres, enzymes, many hormones (such as insulin) and they are involved in the storage and transportation of substances around the body (haemoglobin in red blood cells is a protein that binds oxygen molecules for example).
There are 20 naturally occurring amino acids of which 9 are essential in humans. Essential amino acids cannot be synthesised by the body and must be consumed in food. Non-essential amino acids are synthesised from essential amino acids and carbohydrates.
The most common amino acids are ⍺-amino acids and they have a general structure:
The difference between the ⍺-amino acids is in the nature of the R group or side chain (see below).
β-amino acids and ɣ-amino acids are less common:
Although most amino acids have a systematic name (alanine is 2-aminopropanoic acid) they are referred to by their common names or even abbreviations of their common names for ease.
At a specific pH known as the isoelectric point, the two functional groups in an amino acid interact to give a structure known as a zwitterion. The amine group behaves as a base accepting a proton from the acidic carboxylic acid group, and as a result amino acids are very soluble in water (they are essentially ionic).
Each amino acid has a unique isoelectric point e.g. pH 5.97 for valine and pH 2.76 for aspartic acid. An amino acid is electrically neutral at its isoelectric point and will not migrate in an electric field (this is an important consideration when separating amino acids or polypeptide fragments using the analytical technique of electrophoresis).
In general, we find that the more basic the R group an amino acid, the higher the pH of the isoelectric point.
[Essentially this is because the isoelectric point is the average of the pKa values for the ammonium and carboxylate groups of the zwitterion and well as the pKa for any acidic or basic R groups. If you are super-interested in taking this further, check out this page from Chem.LibreTexts.org.]
Aqueous solutions of amino acids behave as buffers (different amino acid solutions act as effective buffers over differing pH ranges depending on their isoelectric point) . Adding small amounts of acid or alkali to the aqueous amino acid causes almost no change in pH as the zwitterions can lose or gain protons …
We can investigate the buffering capacity of an aqueous solution of an amino acid by measuring how the pH changes as either HCl(aq) or NaOH(aq) is added. Consider the titration curve for glycine shown below:
At pH 2.3 enough acid has been added for half the zwitterions to be converted into H3N+CH2COOH
H3N+CH2COO–(aq) + H3O+(aq) ⇌ H3N+CH2COOH(aq) + H2O(l)
At pH 10.6 enough alkali has been added for half the zwitterions to be converted into H2NCH2COO–
H3N+CH2COO–(aq) + OH–(aq) ⇌ H2NCH2COO–(aq) + H2O(l)
We can see from the titration curve that glycine is a good buffer at / near both of these pH as addition of further H3O+ or OH– causes little overall change in pH (there is an equal ratio of HA : A–), whereas it is a very poor buffer at / near its isoelectric point as a small addition of H3O+ or OH– leads to a large change in pH.
The importance of different R groups
The physiological pH of the human body is pH 7.4. At this pH, the R groups of some amino acids are polar and charged, some are polar but uncharged, some have non-polar (hydrophobic) R groups and some are not so easily categorised. It helps to sort amino acids into these groupings so that we can more easily see how important these R groups are in determining the 3D structure of a protein, the nature of the active site in enzymes and other biochemical properties.
- amino acids with polar, charged R groups at pH 7.4 (these R groups aid the solubility of proteins if they are on the surface of the protein, and are also involved in electrostatic attractions and repulsions between polypeptide chains that help determine the tertiary structure of a protein)
- amino acids with polar, uncharged R groups at pH 7.4 (these R groups can form hydrogen bonds with water)
- amino acids with non-polar R groups at pH 7.4 (these R groups are the key drivers of the folding of a polypeptide chain into its tertiary structure)
- and the rest
All ⍺-amino acids (except for glycine) are optically active as the ⍺-carbon atom is chiral.
Dipeptides and polypeptides
Amino acids can link together to form dipeptides and polypeptides via a series of condensation reactions between the amine functional group of one amino acid and the carboxylic acid functional group of another. This reaction forms an amide / polyamide but in the context of amino acids and proteins, it is called a peptide link.
Peptide links can be hydrolysed by refluxing the protein or polypeptide with a strong acid or alkali. In either case, we form salts of the amino acids.
Practice questions
- With reference to the structures described above, give the systematic names of the following amino acids (not the zwitterions!) :
(a) glycine
(b) serine
(c) phenylalanine
(d) lysine
(e) valine
- Explain why glycine has a considerably higher melting point than organic molecules with similar molar masses:
| Substance | Mr / g mol-1 | Melting point / °C |
|---|---|---|
| glycine | 75 | 235 |
| propanoic acid | 74 | – 21 |
| 1-aminobutane | 73 | – 49 |
- Asparagine has an isoelectric point of 5.41.
(a) Explain what is meant this statement.
(b) Draw the structure of asparagine at pH 2, pH 5.41 and pH 11.
- The tripeptide shown below is a common antioxidant. Draw the products of the reaction when it is refluxed with a solution of moderately concentrated sodium hydroxide.
- Draw the repeat unit of a polypeptide formed from one monomer of threonine and one monomer of histidine, given the structures of their respective ions:
Answers
- (a) aminoethanoic acid
(b) 2-amino-3-hydroxypropanoic acid
(c) 2-amino-3-phenylpropanoic acid
(d) 2,6-diaminohexanoic acid
(e) 2-amino-3-methylbutanoic acid
2. Glycine exists as a zwitterion, NH3+CH2COO–, with very strong ionic bonds between ions in the crystal. There is some hydrogen bonding in 1-aminobutane and propanoic acid as well as London forces but these intermolecular bonds are far weaker than ionic bonds, needing far less energy to break, hence the much lower melting points.
3. (a) The isoelectric point is the pH at which an amino acid exists in the form a zwitterion and is electrically neutral (acidic or basic R groups are neutral / uncharged at this pH).
(b)
4.
5.
