Key facts
- Core groups
- Amino group, carboxyl group, hydrogen, side chain (R group)
- Standard set
- 20 genetically encoded amino acids
- Additional encoded
- Selenocysteine (Sec, U) and pyrrolysine (Pyl, O)
- Configuration in proteins
- L-form; glycine is achiral
- Linkage
- Peptide (amide) bond, releasing one water molecule
- Notation
- Three-letter and one-letter codes (IUPAC-IUB)
Understanding Amino Acids
Amino acids are small organic molecules with two defining functional groups: an amine (-NH2) and a carboxylic acid (-COOH). Peptides and proteins are built from them. In the alpha-amino acids that make up proteins, both groups hang off the same carbon atom, which is called the alpha carbon.
Hundreds of amino acids have been found in nature, yet cells use only a small set of them to build proteins [2]. These go by several names: standard, canonical or proteinogenic. So when someone in peptide research asks what are amino acids, they nearly always mean this set of 20. Plenty of others turn up in metabolism or in synthetic peptides without being encoded by the genetic code. Ornithine, citrulline and norleucine are three examples.
What Is the Structure of an Amino Acid?
All standard amino acids share the same backbone layout. An alpha carbon is bonded to four things: an amino group, a carboxyl group, a hydrogen atom and a side chain, usually called the R group.
Only the side chain changes from one standard amino acid to the next, so it sets the size, charge, polarity and reactivity. Glycine's side chain is a single hydrogen atom. Tryptophan's is a bulky two-ring indole group. Cysteine has a thiol (-SH) that can bond to a second cysteine and form a disulfide bridge.
Dissolve an amino acid in water near neutral pH and the amino group usually picks up a positive charge (-NH3+) while the carboxyl group carries a negative one (-COO-). A molecule holding both charges at once is called a zwitterion. Some side chains have acidic or basic groups of their own, and they add more charges; that's why a peptide's net charge depends on both its composition and the pH.
Why Do Amino Acids Have L and D Forms?
The two forms exist because, in every standard amino acid except glycine, the alpha carbon carries four different groups. That makes it a chiral center, with two possible arrangements that are mirror images of each other.
Ribosomes build proteins from L-amino acids, and cells run proofreading steps that help keep D-amino acids out of new proteins [5]. That doesn't make D forms irrelevant to research. Synthetic peptides sometimes include them on purpose: SS-31 starts with D-arginine, PT-141 contains D-phenylalanine, and in each case the D residue is part of what defines the compound. One practical catch is that L and D forms weigh the same, so mass spectrometry on its own can't distinguish them.
How Are Amino Acids Classified?
The usual way to classify amino acids is by side-chain chemistry. That sorts them by how they behave around water and around each other.
| Group | Amino acids | Shared feature |
|---|---|---|
| Nonpolar, aliphatic | Glycine, alanine, valine, leucine, isoleucine, methionine, proline | Hydrocarbon or thioether side chains; tend to avoid water |
| Aromatic | Phenylalanine, tyrosine, tryptophan | Ring structures that absorb ultraviolet light |
| Polar, uncharged | Serine, threonine, cysteine, asparagine, glutamine | Can form hydrogen bonds with water |
| Positively charged (basic) | Lysine, arginine, histidine | Side chains that accept protons |
| Negatively charged (acidic) | Aspartic acid, glutamic acid | Side chains with a carboxyl group |
Different fields sort them differently. Nutrition science splits essential amino acids, the ones the human body can't make in sufficient amounts, from nonessential ones. Nine usually make the essential list: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine [4]. Analytical chemists care about other things, such as hydrophobicity and UV absorbance, since those decide how a peptide behaves on an HPLC column.
Some organisms encode two more amino acids by reinterpreting stop codons. Selenocysteine (Sec, U) occurs in humans, and pyrrolysine (Pyl, O) occurs in certain archaea and bacteria [3]. You will sometimes see them called the 21st and 22nd amino acids.
How Are Amino Acids Written?
The standard abbreviations, in both three-letter and one-letter form, were set out by the IUPAC-IUB Joint Commission on Biochemical Nomenclature [1].
Three-letter codes like Gly, Lys and Trp are easy to read. One-letter codes like G, K and W keep long sequences short. Some single letters follow the name (A for alanine, G for glycine), and some don't (K for lysine, W for tryptophan, D for aspartic acid). All 20 codes are listed on the Amino Acids hub, and related terms are defined in the Peptide Glossary.
The same recommendations include codes for uncertainty. B (Asx) stands for aspartic acid or asparagine, Z (Glx) for glutamic acid or glutamine, and X for an unknown or unspecified residue. You'll meet them when a method can't tell two residues apart, for instance after acid hydrolysis has turned asparagine into aspartic acid [1].
Amino-Acid Sequences
An amino-acid sequence is the order of amino acids along a peptide or protein chain. By convention it is written from the N-terminus to the C-terminus.
Nothing describes a peptide's identity more basically than its sequence. Take KPV, which is lysine-proline-valine. Reverse it to VPK and you have a different molecule, with a different free amino end. Peptide sequences goes further into reading sequences, modified residues included.
What Is a Peptide Bond?
A peptide bond is the amide bond formed when one amino acid's carboxyl group reacts with the next one's amino group. Each bond releases one molecule of water.
Since every link costs a water molecule, an amino acid inside a chain (its residue mass) weighs about 18 Da less than it does free. Free glycine is 75.07 g/mol, for example, but a glycine residue adds only 57.05 to a chain. This is the arithmetic behind expected peptide masses in mass spectrometry. The bond is also rigid and flat, and that shapes how chains fold. The peptide bonds article explains it fully.
Amino Acids, Peptides and Proteins
The three terms climb in scale. An amino acid is one unit. A peptide is a short chain of them. A protein is a long chain, or a group of chains, folded into a defined three-dimensional structure.
No universal length marks the point where a peptide turns into a protein, and each field draws the line a little differently. Glutathione is a tripeptide, MOTS-c has 16 residues and sermorelin has 29; many proteins run to hundreds. For the full distinction, read peptides vs proteins.
Why Does Sequence Matter?
Two chains with the same number of amino acids, even the very same set of them, can be completely different molecules if the order changes.
- Identity: the sequence, plus any modifications, is what defines which compound a sample is.
- Structure: the order of side chains decides how a chain folds and which groups end up side by side.
- Analysis: isomeric sequences have identical masses, so you need tandem mass spectrometry or chromatography to confirm the order.
- Synthesis: methods like solid-phase peptide synthesis add residues one at a time in a fixed order, and a single misplaced step gives a different product.
FAQFrequently asked questions
What are amino acids?
Amino acids are organic molecules built around a central alpha carbon that holds an amino group, a carboxyl group, a hydrogen atom and a side chain. Peptides and proteins are made from them. The genetic code encodes twenty standard amino acids, and each one's side chain gives it its own size, charge and polarity.
How many amino acids are there?
Hundreds occur in nature, but the standard set that the genetic code uses for protein synthesis is 20. Some organisms encode two more, selenocysteine and pyrrolysine, by recoding stop codons. Beyond that, synthetic chemistry contributes many non-standard residues, norleucine among them, that show up in research peptides.
What is the difference between an amino acid and a peptide?
An amino acid is one molecular unit. A peptide is a chain of two or more amino acids linked by peptide bonds in a specific order; two residues make a dipeptide, three a tripeptide. Once an amino acid is linked into the chain we call it a residue, because it has lost the atoms of one water molecule.
What are essential amino acids?
In nutrition science, they're the amino acids the human body can't make in sufficient amounts. Nine usually make the list: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine. It's a nutritional label, though. Chemically, they're ordinary standard amino acids without any special structural feature.
Why are amino acids in proteins L-amino acids?
All standard amino acids except glycine have a chiral alpha carbon, so each can exist as an L or a D mirror image. Ribosomes build proteins from the L forms, and cellular proofreading helps keep D forms out. Synthetic peptides can include D-amino acids deliberately, and when they do, that choice becomes part of the compound's defined identity.
What is an amino acid residue?
It's an amino acid as it exists inside a peptide chain. Each peptide bond that forms removes one water molecule, so a residue weighs about 18 Da less than the free amino acid. To get the expected mass of a linear peptide, you add up the residue masses and then add back one water.
REFScientific references
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IUPAC-IUB JCBN. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature and symbolism for amino acids and peptides. Recommendations 1983. Biochem J. 1984;219(2):345-73. PubMed 6743224
reference standard, nomenclature recommendations -
Wu G. Amino acids: metabolism, functions, and nutrition. Amino Acids. 2009;37(1):1-17. PubMed 19301095
review -
Ambrogelly A, et al. Natural expansion of the genetic code. Nat Chem Biol. 2007;3(1):29-35. PubMed 17173027
review -
Lopez MJ, et al. Biochemistry, Essential Amino Acids (Archived). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024. NCBI Bookshelf NBK557845. PubMed 32496725
textbook chapter, NCBI Bookshelf (StatPearls) -
Kuncha SK, et al. Chiral checkpoints during protein biosynthesis. J Biol Chem. 2019;294(45):16535-16548. PubMed 31591268
review
Research Library: Peptide Fundamentals
Research Library: Peptide Fundamentals