Selenocysteine: What is an example of a non standard amino acid?

December 24, 2025 •

3 min read

While the universal genetic code typically accounts for 20 standard amino acids, some proteins incorporate additional, non-standard variants during or after translation. A prime example of a non standard amino acid that is genetically encoded is selenocysteine, often referred to as the '21st amino acid'.

Quick Summary

Selenocysteine is a non-standard amino acid containing selenium that is incorporated directly into proteins during synthesis by recoding a stop codon. This process requires a unique insertion sequence and special translational machinery. Other non-standard amino acids, like hydroxyproline, are formed via post-translational modification.

Key Points

Selenocysteine: A non-standard amino acid containing selenium, it is incorporated directly into proteins during synthesis by recoding the UGA stop codon.
Post-Translational Modification: Some non-standard amino acids, like hydroxyproline in collagen, are formed by modifying a standard amino acid after protein synthesis is complete.
Metabolic Intermediates: Other non-standard amino acids, such as ornithine and citrulline, are not found in proteins but are crucial for metabolic cycles like the urea cycle.
Genetic Flexibility: The existence of selenocysteine and pyrrolysine demonstrates that the genetic code can be expanded beyond the 20 standard amino acids, utilizing special mechanisms for their insertion.
Unique Functionality: Non-standard amino acids often provide unique chemical properties essential for specialized protein functions, such as antioxidant activity in selenoenzymes or structural stability in collagen.

Defining a Non Standard Amino Acid

Non-standard amino acids are a diverse group of amino acids that do not fit the criteria of the 20 standard, or proteinogenic, amino acids directly encoded by the canonical genetic code. Their presence in proteins or biological systems arises from different mechanisms, broadly categorized into two main groups: those incorporated during translation via special recoding events, and those formed by chemical modification of a standard amino acid after protein synthesis (post-translational modification).

Unlike non-essential amino acids, which are standard building blocks that the body can synthesize, non-standard amino acids offer unique chemical properties that are often vital for specific protein functions or metabolic pathways. Their existence expands the functional possibilities of the proteome beyond what the standard 20 amino acids can achieve alone.

Example 1: Selenocysteine, the 21st Amino Acid

The most fascinating example of a non standard amino acid is selenocysteine, which is incorporated directly into the polypeptide chain during protein synthesis. Its unique mechanism challenges the traditional understanding of the genetic code:

The UGA Codon Recoding

In most organisms, the codon UGA acts as a 'stop' signal, terminating translation. However, in organisms that synthesize selenoproteins, this codon can be 'recoded' to specify selenocysteine instead of a stop. This process is dependent on a specific transfer RNA (tRNASec) and a hairpin-like RNA structure called the Selenocysteine Insertion Sequence (SECIS). The location of the SECIS element can vary between eukaryotes and bacteria. This mechanism ensures targeted insertion of selenocysteine, which, due to its selenium atom, provides powerful antioxidant properties to selenoenzymes.

Example 2: Hydroxyproline from Post-Translational Modification

Another major category of non-standard amino acids is formed by altering a standard amino acid after it has been incorporated into a protein. Hydroxyproline is a prime example, crucial for collagen. It is formed when specific proline residues in collagen are modified by prolyl hydroxylase, adding a hydroxyl group. These hydroxyl groups are vital for stabilizing collagen's triple-helix structure through hydrogen bonding.

Example 3: Non-Protein Intermediates Like Ornithine

Some non-standard amino acids function primarily as free molecules in metabolic roles. Ornithine is one such example. It is a key intermediate in the urea cycle, converting ammonia into urea. Citrulline is another non-standard amino acid involved in this pathway.

Comparison of Standard and Non Standard Amino Acids


Feature	Standard Amino Acids (e.g., Leucine)	Selenocysteine (Non-Standard)	Hydroxyproline (Non-Standard)
Genetic Encoding	Coded directly by universal genetic codons.	Coded by a special recoding of a stop codon (UGA).	Not genetically encoded.
Incorporation	Directly incorporated during ribosomal translation.	Inserted during translation using special machinery.	Formed via post-translational modification of proline.
Occurrence	Common in all living organisms and proteins.	Rare, found in specific selenoenzymes.	Found primarily in collagen and other structural proteins.
Chemical Basis	Typically contain carbon, hydrogen, oxygen, nitrogen, and sometimes sulfur.	Contains a selenium atom instead of sulfur, similar to cysteine.	A modified proline residue with an added hydroxyl group.
Functional Role	General building block of all proteins.	Critical for catalytic activity in redox enzymes.	Essential for collagen stability and strength.

Why Understanding Non-Standard Amino Acids Matters

Understanding non-standard amino acids highlights the flexibility and complexity of biological systems. They enable:

Expanded Functionality: The unique atoms or modifications in non-standard amino acids provide proteins with a wider range of capabilities, crucial for tasks like antioxidant defense or structural integrity.
Metabolic Specialization: Amino acids like ornithine demonstrate how specialized pathways handle critical metabolic processes.
Bioengineering Applications: Knowledge of non-standard amino acids, especially those with special incorporation methods, has advanced genetic code expansion, allowing for the creation of novel biomaterials and therapies. More information on genetic code expansion is available on the National Institutes of Health (NIH) website.

Conclusion

In summary, a non standard amino acid is any amino acid not included in the standard 20. Selenocysteine is a key example, directly incorporated into proteins through a special recoding mechanism. Others, like hydroxyproline, are formed after protein synthesis, while some, such as ornithine, act as metabolic intermediates. Their diverse roles and synthesis methods showcase the adaptability of biological systems and offer significant potential for scientific advancements.

Frequently Asked Questions

Essential amino acids cannot be synthesized by the body and must be obtained from the diet. Non-essential amino acids can be synthesized internally. Non-standard amino acids are any amino acids outside of the 20 standard protein-building ones, regardless of whether the body can make them.

Selenocysteine insertion relies on a special mechanism called translational recoding. A specific RNA hairpin structure, the SECIS element, is present in the mRNA, and a dedicated elongation factor delivers a special tRNA molecule carrying selenocysteine to the UGA codon.

Yes, pyrrolysine is another example. It is the 22nd proteinogenic amino acid and is found in some archaea and bacteria, where it is incorporated in response to the UAG stop codon, another example of translational recoding.

Hydroxyproline, a non-standard amino acid formed from proline after translation, is critical for stabilizing the triple-helical structure of collagen. The hydroxyl groups form hydrogen bonds that strengthen the protein's overall structure.

No. While some, like selenocysteine and hydroxyproline, are found in proteins, others, such as ornithine and citrulline, exist as free molecules that function as metabolic intermediates in pathways like the urea cycle.

Post-translational modification (PTM) is the process by which a newly synthesized protein is chemically altered. This can involve the addition of chemical groups like hydroxyls or phosphates, which can change an amino acid into a non-standard one.

Studying non-standard amino acids is crucial for understanding specialized protein functions, metabolic pathways, and the full diversity of molecular biology. It also has significant applications in bioengineering, allowing for the design of novel proteins and biomaterials.