BIOSYNTHESIS OF NONESSENTIAL AMINO ACID

Clinical biochemistry second stage lecture 5 Amino acid metabolism

BIOSYNTHESIS OF NONESSENTIAL AMINO ACID
Nonessential amino acids are synthesized from intermediates of metabolism or, as in the case of tyrosine and cysteine, from essential amino acids. Two amino acids—histidine and arginine—are generally classified as nonessential. However, their normal concentrations are limiitin, and, during periods of tissue growth (for example, in children or in individuals recovering from wasting diseases), histidine and arginine need to be supplemented in the diet. [Note: Some amino acids found in proteins, such as hydroxyproline and hydroxylysine are modified after their incorporation into the protein .
A. Synthesis from ?-keto acids. Alanine, aspartate, and glutamate are synthesized by transfer of an amino group to the ?-keto acids, pyruvate, oxaloacetate, and ?-keto-glutarate, respectively. These transamination reactions are the most direct of the biosynthetic pathways. Glutamate is unusual in that it can also be synthesized by the reverse of oxidative deamination, catalyzed by glutamate dehydrogenase


Pyridoxal Phosphate: In a transamination reaction, i.e. reactions involving the transfer of the ? -amino group of an amino acid to the ? -carbon of a keto acid, thereby forming a new amino acid and a new keto acid. Pyridoxal phosphate (vitamin B6) acts as an intermediate carrier of the amino group that is being transferred.

B Synthesis by amidation
1.Glutamine:.
This amino acid, which contains an amide linkage with ammonia at the ?-carboxyl, is formed from glutamate by glutamine synthetasThe reaction is driven by the hydrolysis of ATP. In addition to producing glutamine for protein synthesis, the reaction also serves as a major mechanism for the detoxification of ammonia in brain and liver

2. Asparagine: This amino acid, which contains an amide linkage with ammonia at the ?-carboxyl, is formed from aspartate by asparagine synthetase, using glutamine
as the amide donor. The reaction requires ATP, and, like the synthesis of glutamine, has an equilibrium far in the direction of asparagine synthesis.

C. Proline
Glutamate is converted to proline by cyclization and reduction reaction

D. Serine, glycine, and cysteine

1. Serine arises from 3-phosphoglycerate an intermediate in glycolysis, which is first oxidized to phosphopyruvate, and then transaminated to 3-phosphoserine. Serine is formed by hydrolysis of the phosphate ester. Serine can also be formed from glycine through transfer of hydroxymethyl group




2. Glycine is synthesized from serine by removal of a hydroxy-methyl group, also by serine hydroxymethyl transferase (see Figure 20.6A).
3. Cysteine is synthesized by two consecutive reactions in which homocysteine combines with serine, forming cystathionine, which, in turn, is hydrolyzed to ?-ketobutyrate and cysteine (see Figure 20.8). Homocysteine is derived from methionine. Because methionine is an essential amino acid, cysteine synthesis can be sustained only if the dietary intake of methionine is adequate




E. Tyrosine
Tyrosine is formed from phenylalanine by phenylalanine hydroxylase. The reaction requires molecular oxygen and the coenzyme tetrahydrobiopterin,. One atom of molecular oxygen becomes the hydroxyl group of tyrosine, and the other atom is reduced to water. During the reaction, tetrahydrobiopterin is oxidized to dihydrobiopterin. Tetrahydrobiopterin is regenerated from dihydrobiopterin in a separate reaction requiring NADPH. Tyrosine, like cysteine, is formed from an essential amino acid and, is therefore, nonessential only in the presence of adequate dietary phenylalanine.