Amino Acid Biosynthesis

The biosynthesis of each Amino acid is carried out in a unique pathway from that of another. This is because each of the amino acid, especially the 20 common amino acids, has a distinct structure. However, some generalities do apply to both the synthesis and the degradation of all amino acids.

Essential and nonessential amino acids

The 20 amino acids found in human body can be classified into essential and nonessential amino acids.

Essential amino acids are those that must be present in a diet, and which the body cannot synthesize. They include:

  • Arginine
  • Histidine
  • Isoleaucine
  • Leucine
  • Lycine
  • Methionine
  • Threonine
  • Phenylalaine
  • Tryptophan
  • Valine

The pathway for the synthesis of essential amino acids are found in plants and in bacteria, but not in animals.

Nonessential amino acids need not be present in the diet. They are basically synthesized by the human body. These amino acids are

  • Alanine
  • Asparagine
  • Aspartate
  • Cysteine
  • Glutamate
  • Glutamine
  • Glycine
  • Hydroxyproline
  • Hydroxylysine
  • Proline
  • Serine
  • Tyrosine

Important coenzymes in amino acids synthesis

Pyridoxal phosphate  Pyridoxal phosphate is derived from vitamin B6. It is involved in the removal of amino groups through transamination reactions and in donation of amino groups for various amino acid biosynthetic pathways. It is also required for certain reactions that involve the carbon skeleton.

Tetrahydrofolate (FH4) is a coenzyme that is involved in the transfer of one-carbon group at various oxidation states. FH4 is used in both amino acid degradation (e.g. Serine and Histidine) and biosynthesis (e.g. Glycine).

Tetrahydrobiopterin (BH4) BH4is a cofactor that is required or ring hydroxylation reactions (e.g. Phenylalanine to Tyrosine)

Biosynthesis of Amino Acids

 

Glutamate The amino acid biosynthesis of glutamate catalyzed by the transfer of an amino group to the α-ketoglutarate by glutamate dehydrogenase, a mitochondrial enzyme, in what is termed reductive amination reaction. The reaction strongly favors glutamate formation, which lowers the concentration of cytotoxic ammonium ion.

Alanine and Aspartate Transamination of pyruvate forms alanine while transamination of oxaloacetate forms aspartate. The amino donor may be glutamate or aspartate, and the reaction is catalyzed by the enzyme, aminotransferase.

Asparagine The conversion of aspartate to asparagine is catalyzed by asparagine synthase. It resembles the glutamine synthase reaction; however, glutamine rather than ammonium ion provides the nitrogen. In bacteria, asparagine synthase can also use ammonium ion.

Serine synthesis involves the oxidation of the α-hydroxyl group of 3-phosphoglycerate. The reaction is catalyzed by 3-phosphoglycerate dehydrogenase, which converts 3-phosphoglycerate to 3-phosphohydroxypyruvate. Transamination and subsequent dephosphorylation then forms serine. The hydrolytic removal of the phosphoryl group is catalyzed by phosphoserine hydrolase.

Glycine aminotransferases can catalyze the synthesis of glycine from glyoxylate and glutamate or alanine. Other important routes for glycine formation are from choline and from serine.

Proline The initial reaction converts ϒ-carboxyl group of glutamate to the mixed acid anhydride of glutamate ϒ-phosphate, which is subsequently reduced to glutamate ϒ-semialdehyde, and after cyclization reaction, it is reduced to L-proline.

Cysteine is formed by conversion of methionine to homocysteine. Homocysteine and serine form cystathionine, whose hydrolysis forms cysteine and homoserine. Cystathionine formation is catalyzed by cystathionine β-synthase.

Tyrosine The conversion of phenylalanine to tyrosine involves two distinct enzymatic activities. In the first activity, O2 is reduced to H2O and phenylalanine to tyrosine while in the second activity, dihydrobiopterin is reduced by NADPH.