Explore of Non-Protein Amino Acids

“A modified non protein amino acid plays a significance task in metabolite”

A diverse organism of living things and its diverse mammoth metabolite pathways aren’t enough to express through just 20 amino acids, so nature also opens the windows for modified non-protein amino acids to also express in the cellular system significantly. Non-protein amino acids (NPAAs), as opposed to the 20 standard proteinogenic amino acids (L-amino acids incorporated into proteins), do not directly contribute to protein synthesis.

Despite not being proteins, NPAAs can serve a variety of biological functions in living organisms. NPAAs are classified into two types: natural NPAAs and synthetic NPAAs. Approximately 800 naturally occurring NPAAs have been discovered, as well as thousands of chemically modified amino acids.

What is the process behind the creation of non-protein amino acids?

Natural non-protein amino acids are formed via a variety of biosynthetic pathways distinct from those used to produce standard proteinogenic amino acids. They are produced during secondary metabolism in plants, microorganisms, and some animals. These amino acids are frequently derived from alterations in protein-building amino acids or through unique pathways involving metabolic intermediates, such as the tricarboxylic acid (TCA) cycle.

Environmental factors such as stress and nutrient availability can stimulate their production. Non-protein amino acids play important roles in defence mechanisms, plant communication, and nitrogen storage, and some have medicinal properties, such as L-DOPA or beta-alanine. A variety of synthetic NPAAs are derived from natural amino acids and can be produced chemically, biocatalytically, or a combination of the two. Numerous chemical reactions can occur, including alkylation, amination via tandem processes, reductions or alkylations, carboxylation, cyanation combined with hydrolysis, and various side chain modifications.

Significance of Non-Protein Amino Acids

1. Structural Differences
   NPAAs have a similar basic structure to proteinogenic amino acids, but they are not used by ribosomes during translation to produce protein.
2. Biological Roles
   • Signalling molecules: Some NPAAs function as neurotransmitters (e.g., gamma-aminobutyric acid or GABA) or plant signalling molecules (e.g., azetidine-2-carboxylic acid). GABA (gamma-aminobutyric acid) acts as an inhibitory neurotransmitter in the brain.
   • Metabolic intermediates: NPAAs can serve as intermediates in metabolic pathways.
   • Toxins/Defence Compounds: Certain plants produce NPAAs to defend themselves against herbivores (for example, canavanine, a structural analogue of arginine). Ornithine and citrulline are used in the urea cycle to detoxify ammonia. Beta-alanine, a vitamin pantothenic acid (B5) component and carnosine precursor, plays a role in muscle endurance.
3. NPAAs impact on living organisms
   • Some NPAAs can be toxic if incorporated into proteins or due to their structural similarity to proteinogenic amino acids, which can disrupt metabolic functions. In plants, NPAAs may be part of their chemical defence mechanisms. NPAAs are found in a variety of organisms, including bacteria, plants, and animals, and have diverse physiological and ecological roles.

Some Examples of Non-Protein Amino Acids Include:

1. Ornithine: Involved in the urea cycle.
2. Citrulline: Also, a part of the urea cycle.
3. GABA (Gamma-aminobutyric acid): A neurotransmitter in the brain.
4. Taurine: Involved in bile salt formation.
5. β-Alanine: A component of the dipeptide carnosine which is a rate-limiting precursor of carnosine
6. L-DOPA (Levodopa): A precursor to dopamine, used in the treatment of Parkinson’s disease.
7. Sarcosine (N-methylglycine): An intermediate in glycine metabolism.
8. L-Canavanine: Found in certain leguminous plants, an analogue of arginine.
9. Hypoglycine A: Found in unripe ackee fruit, can cause toxicity. It is causative agent of Jamaican vomiting sickness
10. Lanthionine: Occurs in certain bacteria and peptides like antibiotics.
11. Aminoisobutyric acid (AIB): Found in certain metabolic processes. Rare in nature, found in some antibiotics of fungal origin.
12. β-Aminoisobutyric acid (BAIB): A product of pyrimidine catabolism. It is secreted by skeletal muscles on vital body workout or regular exercise
13. Selenocysteine: The 21^st amino acid, present in selenoproteins. Found in the catalytic sites of selenoproteins, which are enzymes that perform oxidation/reduction functions.
14. Cycloleucine: Used in biochemical research, inhibits certain enzymes. It is used in biochemical experiments as a reversible inhibitor of nucleic acid methylation. It’s also a useful building block for pharmaceuticals
15. Pipecolic acid: Involved in the metabolism of lysine. Pipecolic acid is a key intermediate in the synthesis of many natural alkaloids and drugs.

These amino acids have diverse roles in metabolism, signalling, and various physiological processes.