14. Synthesis of non-essential amino acids

Page created on March 14, 2018. Last updated on December 18, 2024 at 16:55

Learning objectives

• What does it mean that an amino acid is non-essential?
• What does it mean that an amino acid is conditionally essential?
• What does it mean that an amino acid is essential?
• Which amino acids are non-essential?
• Which amino acids are conditionally essential?
• Which amino acids are essential?
• Which types of biochemical reactions are important in synthesis of amino acids?
• How is the synthesis of amino acids regulated?

Essential and non-essential amino acids

Essential amino acids are those which the body cannot synthesise on its own, meaning that we must acquire it through diet. Non-essential amino acids are those which the body can synthesise in large amounts. Conditionally essential amino acids are those amino acids which can be synthesised by the body, but not always in large enough amounts required, especially during childhood.

The non-essential amino acids are alanine, aspartate, asparagine, glutamate, serine. The conditionally essential amino acids are proline, arginine, glycine, cysteine, glutamine, and tyrosine. The essential amino acids are histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine.

Nitrogen metabolism

Nitrogen fixation refers to the process where molecular nitrogen (N₂) is converted into ammonia. The bond between nitrogen atoms in N₂ gas is very strong. That means that it requires a lot of energy to break. In biological systems, it needs 16 ATP and 8 electrons. This occurs in certain bacteria but not in humans.

In humans, the most important reaction for incorporating ammonia into organic molecules is the glutamine synthetase, which incorporates ammonia in glutamate to give glutamine.

Biosynthesis of amino acids

Many different reactions are involved in the biosynthesis of amino acids. The main classes of reactions are:

• Transamination reactions (use PLP)
• One-carbon group transfer reactions (use THF, adoMet)
• Glutamine amidotransferase reactions

Glutamine amidotransferase transfers the amino group from glutamine to another molecule.

The synthesis of amino acids takes place mostly in the liver.

PRPP

PRPP (phosphoribosyl pyrophosphate) is an important molecule in the biosynthesis of histidine, tryptophan and nucleotides. PRPP is synthesised by PRPP synthetase.

Biosynthesis of glutamate

Glutamate is synthesised by transamination (aminotransferase) of α-ketoglutarate, often by ALT or AST. It can also be synthesised by glutamine dehydrogenase, but this pathway is less important in humans.

Biosynthesis of glutamine

Glutamine is synthesised from glutamate and ammonia with the glutamine synthetase reaction. This enzyme is allosterically inhibited by 8 molecules, all of them being downstream products. This is a form of negative feedback inhibition. Glutamine synthetase is also covalently regulated, but not by phosphorylation, which is the norm. This enzyme is instead covalently regulated by adenylation.

Biosynthesis of proline

In bacteria proline is synthesised from glutamate. In humans, it’s synthesised by arginine.

Proline is a special amino acid in that it exists in both trans and cis conformations, unlike other amino acids. Proline residues are found in collagen and HIF-1α, for example. These residues are hydroxylated by proline hydroxylase.

Biosynthesis of arginine

Arginine is synthesised from glutamate. Glutamate is converted into ornithine, which enters the urea cycle. Arginine is an intermediate in the urea cycle.

Biosynthesis of glycine, cysteine and serine

Serine is synthesised from 3-phosphoglycerate in a 3-step process. Serine can then be converted to glycine in 1 step. Serine and homocysteine are converted into cystathionine by cystathionine β-synthetase. One more reaction converts cystathionine into cysteine.

An alternative pathway exists for glycine; glycine synthase, which synthesises glycine from CO2, ammonium, and methylene-THF.

Biosynthesis of alanine, aspartate, and asparagine

Alanine and aspartate are synthesised by alanine aminotransferase and aspartate aminotransferase, respectively. Asparagine is synthesised from glutamine amidotransferase, which transfers the amino group from glutamine to aspartate, forming asparagine.

Biosynthesis of tyrosine

Tyrosine is synthesised from phenylalanine in the phenylalanine hydroxylase reaction.

Regulation of amino acid synthesis

Amino acid synthesis is regulated allosterically. The rate-limiting enzyme is usually the first in the sequence of synthesis, and this enzyme is allosterically inhibited by the final amino acid as a form of negative feedback inhibition.

The synthesis of the non-essential amino acids.

Summary

• What does it mean that an amino acid is non-essential?
  • Non-essential amino acids are those which the body can synthesise in large amounts.
• What does it mean that an amino acid is conditionally essential?
  • Conditionally essential amino acids are those amino acids which can be synthesised by the body, but not always in large enough amounts required, especially during childhood
• What does it mean that an amino acid is essential?
  • Essential amino acids are those which the body cannot synthesise on its own, meaning that we must acquire it through diet.
• Which amino acids are non-essential?
  • Alanine, aspartate, asparagine, glutamine and serine
• Which amino acids are conditionally essential?
  • Proline, arginine, glycine, cysteine, glutamine and tyrosine
• Which amino acids are essential?
  • Histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine
• Which types of biochemical reactions are important in synthesis of amino acids?
  • Transamination reactions (use PLP)
  • One-carbon group transfer reactions (use THF, adoMet)
  • Glutamine amidotransferase reactions
• How is the synthesis of amino acids regulated?
  • The synthesis of non-essential amino acids is regulated by negative feedback of the different amino acids