Glutamine is an amino acid that is derived from glutamate through the action of glutamine synthetase. This reaction is driven by the hydrolysis of ATP and serves as a means of transporting ammonia in a non-toxic form. Asparagine, another amino acid, is formed from aspartate with the help of asparagine synthetase and glutamine as the amide donor. This synthesis also requires ATP and strongly favors amide production. Proline, on the other hand, is synthesized from glutamate via glutamate semialdehyde through a series of cyclization and reduction reactions. Additionally, the semialdehyde can be transaminated to ornithine. Serine, glycine, and cysteine are interconnected in their synthesis pathways. Serine is produced from 3-phosphoglycerate, an intermediate in glycolysis, which is first oxidized to 3-phosphopyruvate and then transaminated to 3-phosphoserine. Serine can also be formed from glycine through the transfer of a hydroxymethyl group by serine hydroxymethyltransferase using N5,N10-MTHF as the one-carbon donor. Glycine, on the other hand, is synthesized from serine by removing a hydroxymethyl group, also catalyzed by serine hydroxymethyltransferase. THF serves as the acceptor for the one-carbon group. Cysteine is synthesized through a two-step process involving the combination of Hcy with serine to form cystathionine, which is then hydrolyzed to α-ketobutyrate and cysteine. It is important to note that Hcy is derived from methionine, and cysteine synthesis relies on an adequate intake of methionine in the diet. Tyrosine, another amino acid, is derived from phenylalanine through the action of PAH. This reaction requires molecular oxygen and the coenzyme tetrahydrobiopterin (BH4), which is synthesized from guanosine triphosphate. The hydroxyl group of tyrosine is derived from one atom of molecular oxygen, while the other atom is reduced to water. BH4 is oxidized to dihydrobiopterin (BH2) during the reaction and is regenerated from BH2 by NADH-requiring dihydropteridine reductase. Tyrosine is considered nonessential only when there is an adequate intake of dietary phenylalanine, as it is derived from an essential amino acid. Amino acid metabolism disorders can occur in various conditions and lead to abnormalities in the synthesis or breakdown of amino acids.
Glutamine: This amino acid, which contains an amide linkage with ammonia at the γ-carboxyl, is formed from glutamate by glutamine synthetase (see Fig. 19.18, p. 256). The 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 transport of ammonia in a nontoxic form. (See p. 256 for a discussion of ammonia metabolism.) 2.
Asparagine: This amino acid, which contains an amide linkage with ammonia at the β-carboxyl, is formed from aspartate by asparagine synthetase, using glutamine as the amide donor. Like the synthesis of glutamine, the reaction requires ATP and has an equilibrium far in the direction of amide synthesis.
C. Proline
Glutamate via glutamate semialdehyde is converted to proline by cyclization and reduction reactions. [Note: The semialdehyde can also be transaminated to ornithine.]
D. Serine, glycine, and cysteineThe pathways of synthesis for these amino acids are interconnected.
1.
Serine: This amino acid arises from 3-phosphoglycerate, a glycolytic intermediate (see Fig. 8.18, p. 101), which is first oxidized to 3phosphopyruvate 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 a hydroxymethyl group by serine hydroxymethyltransferase using N5,N10-MTHF as the one-carbon donor (see Fig. 20.6A). [Note: Selenocysteine (Sec), the 21st genetically encoded amino acid, is synthesized from serine and selenium (see p. 407), while serine is attached to transfer RNA. Sec is found in ~25 human proteins including glutathione peroxidase (see p. 148) and thioredoxin reductase (see p. 297).] 2.
Glycine: This amino acid is synthesized from serine by removal of a hydroxymethyl group, also by serine hydroxymethyltransferase (see Fig. 20.6A). THF is the one-carbon acceptor.
3.
Cysteine: This amino acid is synthesized by two consecutive reactions in which Hcy combines with serine, forming cystathionine, which, in turn, is hydrolyzed to α-ketobutyrate and cysteine (see Fig. 20.8). [Note: Hcy is derived from methionine, as described on p. 264. Because methionine is an essential amino acid, cysteine synthesis requires adequate dietary intake of methionine.]
E. Tyrosine
Tyrosine is formed from phenylalanine by PAH (see p. 263). The reaction requires molecular oxygen and the coenzyme tetrahydrobiopterin (BH4), which is synthesized from guanosine triphosphate. One atom of molecular oxygen becomes the hydroxyl group of tyrosine, and the other atom is reduced to water. During the reaction, BH4 is oxidized to dihydrobiopterin (BH2). BH4 is regenerated from BH2 by NADH-requiring dihydropteridine reductase. Tyrosine, like cysteine, is formed from an essential amino acid and is, therefore, nonessential only in the presence of adequate dietary phenylalanine.
VI. AMINO ACID METABOLISM DISORDERS