Amino Acid Biosynthesis

Amino acids are the building blocks of proteins, which control practically all cellular processes within our bodies. The roles of proteins are critical for the function, structure and regulation of our tissues and organs. There are 20 amino acids that constitute the vast array of chemical versatility seen in the different known proteins.

Carboxylic and amino functional groups are both components found in an amino acid. Where an amino group is bonded directly to the alpha-carbon, the amino acid is called an alpha amino acid.

In every alpha amino acid there is an alpha carbon bonded to a carboxylic group, amino group, hydrogen atom and an R-group that symbolizes an entity unique for every amino acid.

Amino acids may be categorized into three general groups: essential amino acids, nonessential amino acids and conditional amino acids. Essential amino acids are so termed because they cannot be made by our bodies – this is in contrast to nonessential amino acids.

While all amino acids are more or less important for physiological functioning, conditional amino acids are only vital during specific times, such as periods of illness or stress.

Several biochemical pathways are involved in the biosynthesis of amino acids, which includes the assembly of amino acids from other precursors. Amino acids are acquired from the breakdown of proteins in processes like in the digestion of food.

One key difference between the biosynthesis of amino acids and that involving other molecules, such as carbohydrates or lipids, is that amino acid synthesis incorporates nitrogen into the process.

Nitrogen sources

A source of nitrogen is a fundamental part of amino acid synthesis. Glutamine and glutamate are key nitrogen sources in animals, which are regulated by a dynamic duo of enzymes, glutamine synthase and glutamate dehydrogenase, respectively.

In order to acquire the alpha amino group, in most amino acids, a process of transamination between glutamate and an alpha-ketoacid acceptor occurs. Ammonia and alpha-ketoglutarate, with the help of the enzyme glutamate dehydrogenase, are required for the synthesis of glutamate.

The biochemical reaction is a two step process that first involves the formation of a Schiff base between ammonia and the ketone of alpha-ketoglutarate. This Schiff base is then later reduced by a hydride transfer from either NADPH or NADH that forms glutamate.

The stereochemistry of the alpha-carbon is established by the hydride transfer. Only the L-isomer of the glutamate is formed due to the manner in which the glutamate dehydrogenase binds the alpha-ketoglutarate. Glutamine is formed by the incorporation of a second ammonium ion into glutamate by the help of the enzyme glutamine synthase.

Metabolites of other pathways

Humans cannot synthesize half of the 20 amino acids. Unlike humans, bacteria and plants can synthesize all of the 20 amino acids independently. The nonessential amino acids that can be synthesized are done via simple pathways, while the biosynthesis of the essential ones are much more complex.

Amino acid precursors that are used in the synthesis of some other amino acids are aspartate, threonine, phenylalanine, serine and glutamate. Tyrosine can be formed from phenylalanine, whereas cysteine and glycine can be formed from serine. Likewise, aspartate can give rise to asparagine, methionine, lysine and threonine, with the latter being able to form isoleucine.

Alpha-ketoglutarate, oxaloacetate, ribose-5-phosphate and 3-phosphoglycerate are substrates used in reactions to give rise to the amino acids glutamate, aspartate, histidine and serine respectively. Glutamate, once obtained from alpha-ketoglutarate, can form glutamine as well as proline and arginine.

Another substrate, pyruvate, can give rise to alanine, valine and leucine, while erythrose-4-phosphate and phosphoenolpyruvate together give rise to phenylalanine, tyrosine and tryptophan.

135-Overview of Amino Acid Biosynthesis

Sources

  1. http://www.biology.arizona.edu/biochemistry/problem_sets/aa/aa.html
  2. https://www.khanacademy.org/

Last Updated: Jul 19, 2023

Dr. Damien Jonas Wilson

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Dr. Damien Jonas Wilson

Dr. Damien Jonas Wilson is a medical doctor from St. Martin in the Caribbean. He was awarded his Medical Degree (MD) from the University of Zagreb Teaching Hospital. His training in general medicine and surgery compliments his degree in biomolecular engineering (BASc.Eng.) from Utrecht, the Netherlands. During this degree, he completed a dissertation in the field of oncology at the Harvard Medical School/ Massachusetts General Hospital. Dr. Wilson currently works in the UK as a medical practitioner.

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