What exactly are unusual amino acids?

Amongst the 20 common amino acids, there are two non-standard amino acids found in nature, selenocysteine (Sec or U), seen in many prokaryotes, as well as most eukaryotes, and pyrrolysine (Pyl or O), found in archaea and one bacterium. These two are encoded by variant codons and are known to be involved in certain organisms’ genetic coding and protein synthesis. 

Unusual amino acids are a subject of interest in scientific research, as they highlight the diversity and complexity of life’s molecular processes and have implications in fields like biochemistry, molecular biology, and the study of specialised adaptations in various organisms.

What functions do unusual amino acids perform?

Unusual amino acids serve unique and specialised functions in various biological contexts. For instance, selenocysteine and pyrrolysine, not part of the standard genetic code, are crucial in certain organisms for the synthesis of specific proteins. Selenocysteine plays a role in protecting against oxidative stress, while pyrrolysine is involved in the metabolism of methane.

In other instances, research has shown that unusual amino acids can be involved in post-translational modifications, affecting protein structure and function. Hydroxyproline, found in collagen, is an example of this, contributing to the stability of collagen fibres.

These atypical amino acids showcase the adaptability and diversity of life, highlighting how organisms have evolved to utilise them in specific processes, which has significant implications for understanding unique biochemical pathways and adaptations in various organisms.

What are some examples of uncommon amino acids?

From selenocysteine to hydroxyproline, take a look at the intriguing roles these atypical building blocks play in the molecular complexity of life.

Hydroxyproline

Hydroxyproline is found in proteins, notably in collagen, the primary structural protein in connective tissues like skin, cartilage and bones. 

Unlike the 20 standard amino acids, hydroxyproline contains a hydroxyl (-OH) group, which contributes to its unique role in collagen’s stability and structure. During collagen synthesis, enzymes post-translationally modify proline residues into hydroxyproline. This modification strengthens collagen fibres, enhancing their ability to withstand mechanical stress. 

This uncommon amino acid is integral to maintaining the structural integrity of tissues and is often used as a marker in studies related to collagen disorders and connective tissue diseases.

Hydroxylysine

Hydroxylysine is often found in collagen, the structural protein that makes up connective tissues. Similar to the previous hydroxyproline, this amino acid contains a hydroxyl group, contributing to collagen’s stability. 

This amino acid, created through post-translational modifications, strengthens collagen fibres, enhancing their tensile strength. In fact, research has found that hydroxylysine is crucial for maintaining healthy skin, cartilage and bones. And any deficiencies or irregularities in hydroxylysine metabolism can lead to collagen-related disorders, affecting the integrity of connective tissues.

Ornithine

Ornithine is a key component in the urea cycle, which plays a crucial role in ammonia detoxification. It is not directly used in protein synthesis like the 20 standard amino acids but is essential for the conversion of ammonia into urea, which can be safely excreted by the body. This process helps maintain proper nitrogen balance in the body and prevents the toxic build up of ammonia. 

Ornithine is typically used in dietary supplements as it has consistently been shown to reduce ammonia levels in conditions like cirrhosis or certain urea cycle disorders. 

Citrulline

Citrulline is another non-standard amino acid involved in several essential physiological processes. It plays a significant role in the urea cycle, where it assists in the removal of excess ammonia from the body, a critical detoxification process. 

Citrulline is also involved in the synthesis of arginine, another amino acid important for protein synthesis and nitric oxide production, which affects blood vessel dilation and cardiovascular health. 

Due to its superior benefits, citrulline is sometimes used in dietary supplements to support exercise performance, improve blood flow, and reduce muscle fatigue.

What’s the difference between uncommon and unnatural amino acids?

Put simply, the key distinction between uncommon and unnatural amino acids lies in their natural occurrence and intended use, with uncommon amino acids being a part of natural biological processes, and unnatural amino acids being artificially created for specific applications.

Uncommon amino acids are naturally occurring but less frequently found in proteins than the 20 standard amino acids. As shown above, they serve specialised roles in specific biological processes. 

Unnatural amino acids on the other hand, are not naturally-synthesised by living organisms and are chemically engineered or synthesised in a laboratory. In fact, they do not naturally occur in the genetic code. 

Because of this, unnatural amino acids are often used in scientific research and biotechnology to create modified or designer proteins for various purposes, including studying protein structure and function or developing therapeutic applications.

Want to explore amino acid physio-chemical properties? Try our helpful amino acid calculator today.

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