Amino Acid Biosynthesis

Abstract

Amino acids are classically considered as the building blocks for the synthesis of proteins. The unique characteristics of amino acids are the presence of a free amino group in the α‐carbon and a free carboxyl group. The amino acids differ from each other with respect to their side‐chains and are classified into subgroups according to their similarity in carbon skeleton, substituent groups or a common metabolic pathway. The biosynthesis of amino acids involves several biochemical pathways in which amino acids are assembled from other precursors and is distinct from that involving lipids or carbohydrates because it includes the use of nitrogen. In addition to the 20 canonical amino acids that serve as the primary basis of protein structure and function, many noncanonical amino acids are either found in nature or are chemically created by man. Noncanonical amino acids are used as synthetic intermediates or therapeutics and may also be encoded directly into proteins to obtain useful new features, including better protein stability and increased activity.

Key Concepts

  • Amino acids are classically considered as the building blocks from which proteins are synthesised.
  • In addition to their structural role in proteins, the amino acid sequence dictates protein tertiary structure and affects protein function, localisation, recognition and posttranslational modification. In addition, selected amino acids serve as regulators of gene expression and the protein phosphorylation cascade, and play a role in the regulation of protein turnover, signal transduction, transport of nitrogen and carbon across the organs, and neurotransmission.
  • The biosynthesis of amino acids involves several biochemical pathways in which amino acids are assembled from other precursors and is distinct from that involving lipids or carbohydrates because it includes the use of nitrogen.
  • The fixation of nitrogen is a process that converts atmospheric nitrogen to a form that can be used biologically.
  • The pathways for the synthesis of essential amino acids are present only in microorganisms and plants.
  • Nine of 12 nonessential amino acids are synthesised from amphibolic intermediates, whereas three amino acids (tyrosine, cysteine and hydroxylysine) derive from essential amino acids. Amino acid transaminases, glutamate dehydrogenase and glutamine synthetase play a central role in the synthesis of nonessential amino acids.
  • In the human adult, as much as 200–250 g of proteins are degraded daily, and their constituent amino acids are in large part reutilised in protein synthesis.
  • Amino acid deficiency states can result if any of the essential amino acid is present in inadequate amounts or omitted from the diet.
  • Alanine, glutamate and glutamine are crucial links between energy and protein metabolism. Moreover, glutamine and alanine biosynthesis in muscle provides a means for the transport of carbon from peripheral tissues to the liver for gluconeogenesis and nitrogen for ureagenesis.
  • Besides the 20 canonical amino acids, many noncanonical amino acids are either found in nature or are chemically created by man. Noncanonical amino acids are used as synthetic intermediates or therapeutics and may also be encoded directly into proteins to obtain useful new features, including better protein stability and increased activity.

Keywords: proteins; nutrition; nitrogen; carbon; ammonia

Figure 1. The nitrogen cycle. Although some urea can be used, most animals and humans are not able to use inorganic nitrogenous compounds. Therefore, they meet their N requirements by eating bacterial, plant or animal proteins. However, ruminants, which possess a large population of commensal bacteria in their intestines, can use nonamino acid N sources. See also: Rumen
Figure 2. Outline of pathways of synthesis of essential amino acids.
Figure 3. The hydroxylation of phenylalanine to tyrosine. From Scriver CR, Beaudet AL, Sly WS et al. The Metabolic and Molecular Bases of Inherited Disease, 7th edn, chaps 27–38. New York, © 1995 McGraw‐Hill.
Figure 4. The reaction of glutamate dehydrogenase.
Figure 5. The reactions of glutaminase and glutamine synthetase.
Figure 6. Outline of pathways of synthesis of nonessential amino acids. Modified from Munro HM (ed.) (1969) Evolution of protein metabolism in mammals. In: Mammalian Protein Metabolism, vol. 3, pp. 133–182. New York: Academic Press.
Figure 7. Pathways of homocysteine–cysteine metabolism. THF, tetrahydrofolate; B12, vitamin B12 and B6, vitamin B6.
Figure 8. Noncanonical amino acids.
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Further Reading

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Deferrari, Giacomo, Picciotto, Daniela, and Garibotto, Giacomo(Sep 2020) Amino Acid Biosynthesis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0029204]