Amino acids do three main jobs in a cell. They are the twenty building blocks strung into proteins in the order a gene spells out. Several are starting material for other molecules, such as tyrosine for dopamine and melanin. And their ionizable groups, histidine's in particular, help hold pH steady.
- Twenty amino acids are used to build proteins, in an order encoded by a gene.
- PubChem lists tyrosine as a precursor of dopamine, norepinephrine, epinephrine, thyroid hormones and melanin.
- Tryptophan is listed as a precursor of serotonin and, inefficiently in mammals, of niacin.
- Histidine's imidazole side chain has a pKa near 6, the closest of any side chain to neutral pH.
- A residue in a chain weighs about 18 daltons less than the free amino acid because each peptide bond releases one water.
Three jobs, one small molecule
Picture a box of plastic building bricks. Most of the time you snap them together into something bigger. Now and then you melt one down and mold it into a different shape entirely. And a few of the bricks have a hinge that flexes when the room warms up. Amino acids do all three of those things in a cell.
The first job is the famous one: amino acids are the units proteins are built from. The second is less well known. Several amino acids are raw material for other molecules that are not proteins at all, from pigments to signaling molecules. The third job is chemical rather than structural. Amino acids carry groups that can take up or give off a proton, and that lets them soak up small changes in acidity.
This page stays with that cell chemistry. It does not cover diet, nutrition or supplements, and nothing here describes what any amino acid does when taken by a person. For the size question of how a single amino acid relates to a whole protein, the amino acids versus protein guide covers it.
- Build: joined into chains in the order a gene spells out
- Convert: tyrosine, tryptophan and histidine become other molecules
- Buffer: ionizable groups absorb small shifts in acidity
- Differ: side chains give each one its character
Job one: building proteins
The NHGRI glossary calls the amino acid the fundamental molecule that serves as the building block for proteins, and puts the number used for that at twenty. A protein is one or more chains of them, called polypeptides, and the order of amino acids in each chain is encoded in a gene.
That order is the whole point. Twenty different units, joined end to end by peptide bonds, can be arranged in an enormous number of sequences, and the sequence decides how the chain folds and what the finished protein can do. Swap one residue and you have, chemically, a different molecule. Sometimes it behaves almost the same. Sometimes it does not fold at all.
Each unit shares the same backbone, an amino group and a carboxyl group on a central carbon, and differs only in its side chain. The monomers guide goes through why amino acids count as the monomers of proteins, and the side chains are what give the finished chain its character: some water-loving, some greasy, some charged.
A cell reads the gene, builds the chain one residue at a time, and the chain folds. Most of the cell's structural material, most of its enzymes and most of its transport machinery come out of that process.
Job two: starting material for other molecules
Not every amino acid ends up in a protein. Some are converted, step by step, into molecules with a completely different job. PubChem's record descriptions list several of these routes, and a few are worth setting side by side.
| Amino acid | Listed as a precursor of |
|---|---|
| Tyrosine | Dopamine, norepinephrine and epinephrine; thyroid hormones; melanin |
| Tryptophan | Serotonin, by way of 5-hydroxytryptophan; niacin, inefficiently in mammals |
| Histidine | Histamine |
| Glycine | Described as a component and precursor for many macromolecules in cells |
The pattern is that the side chain carries the useful part. Tyrosine's ring, with its hydroxyl group, is the core of the catecholamines and of melanin. Tryptophan's indole ring becomes serotonin's. Histidine's imidazole ring is kept in histamine. The cell trims or adds a few atoms and the amino acid becomes something else.
Glycine is the plain one. PubChem describes it as the simplest proteinogenic amino acid and the only achiral one, with a single hydrogen as its side chain. It is also listed as a signaling molecule in its own right in nerve tissue, which makes it one of the few amino acids that does a job unchanged.
Job three: holding pH steady
Every amino acid has at least two groups that can gain or lose a proton. A few have a third on the side chain. Any group like that resists changes in pH near its own pKa, because a small push of acid or base is absorbed by protons moving on or off the group instead of changing the pH of the solution much.
Most of those groups sit far from neutral. The side-chain carboxyls of aspartic and glutamic acid are around pH 4, and the lysine and arginine side chains are above 10. They are charged at pH 7 but not doing much buffering there, because nothing is shifting.
Histidine is the exception. PubChem lists its imidazole pKa at 5.97, about one unit below neutral. That is close enough that a small fraction of histidines are protonated at pH 7 and the fraction moves when the pH moves. A group that sits near the working pH is the kind that buffers, which is why histidine keeps turning up in discussions of proton handling in proteins.
The acidic and basic amino acids guide has the full table of values and the arithmetic.
How do free amino acids differ from residues in a chain?
The same amino acid behaves differently depending on whether it is loose or locked into a chain. A free amino acid in solution has both its backbone groups exposed and charged, the amine positive and the carboxyl negative. Once it is joined into a peptide, those two groups are used up in the peptide bonds on either side, and only the side chain and the two ends of the whole chain remain ionizable.
That is why chemists write residue for an amino acid inside a chain. Glycine as a free molecule and a glycine residue in a peptide weigh different amounts: forming each peptide bond releases one water, so the residue is lighter by about 18 daltons.
It also explains why the jobs above split cleanly. Building proteins uses amino acids as residues. The precursor routes and much of the buffering chemistry use them as free molecules, or at least as side chains exposed to the solvent.
Reading the jobs off a sequence
A peptide sequence written in one-letter code is a list of residues, and with the three jobs in mind you can read more off it than the length. Count the Y, W and H letters and you know which residues carry the rings that the precursor routes above depend on. Count the D, E, K, R and H letters and you know where the ionizable side chains sit, and so roughly how the chain will behave in a given buffer.
Take GHK, a three-residue sequence this catalog carries. It has one histidine and one lysine. The lysine is positive at pH 7. The histidine is the near-neutral buffering side chain from the section above, and its imidazole ring is also the part PubChem ties to histamine. None of that says anything about what the tripeptide does. It does tell you which parts of the molecule are chemically busy, which is where a lab starts when it plans a method or reads a certificate.
Why does a peptide lab care?
Synthetic peptides are short chains of the same twenty units, and everything above carries straight across. The sequence decides the mass a certificate reports. The side chains decide how the peptide separates on a column, how it ionizes in a mass spectrometer, and which residues are likely to degrade in storage.
Charge matters most on the bench. A peptide rich in lysine or arginine is usually isolated as a salt, paired with counterions from purification, and that extra mass is one reason net peptide content on a certificate is lower than the weight on the label. A peptide with histidine can shift its net charge between two buffers that differ by one pH unit.
None of that requires knowing what the peptide does biologically. It requires knowing what each residue is, which is the reason identity testing leads every good certificate. The R group guide goes deeper on side chains and how a lab sees them.
FOR LABORATORY AND IN-VITRO RESEARCH USE ONLY. NOT FOR HUMAN OR ANIMAL CONSUMPTION.
Common questions
What is the main function of amino acids?
Do amino acids do anything besides make proteins?
Which amino acid is best at buffering near neutral pH?
Is an amino acid the same as a residue?
More science guides
Sources
- National Human Genome Research Institute, Talking Glossary: Amino Acids. Amino acids as the building blocks of proteins; twenty used; sequence encoded in a gene.
- PubChem, L-Tyrosine, record description. Precursor of dopamine, norepinephrine, epinephrine, thyroid hormones and melanin.
- PubChem, L-Tryptophan, record description. Proteinogenic amino acid; precursor of serotonin and, inefficiently, niacin.
- PubChem, L-Histidine, record description. Imidazole side chain; required for the production of histamine.
- PubChem, L-Histidine, dissociation constants. Side-chain pKa listed at 5.97.
- PubChem, Glycine, record description. Simplest and only achiral proteinogenic amino acid; component and precursor of many cell macromolecules.
