BIOSYNTHESIS AND METABOLISM OF AMINO ACIDS

Amino acid biosynthesis is discussed most conveniently in the context of families of amino acids that originate from a common precursor:

1. Glutamate or α-Ketoglutarate Family. Glutamate, glutamine, glutathione, proline, arginine, putrescine, spermine, spermidine, and in yeasts and molds, lysine. A tetrapyrrole (heme) precursor, δ-aminolevulinate, arises from glutamate in some organisms.

2. Aspartate Family. Aspartate, asparagine, threonine, methionine, isoleucine, and, in bacteria, lysine.

3. Pyruvate Family. Alanine, valine, leucine, and isoleucine.

4. Serine-Glycine or Triose Family. Serine, glycine cysteine, and cystine.

In yeasts and molds, mammals, and some bacteria, δ-aminolevulinate is formed by the condensation of glycine and succinate.

5. Aromatic Amino Acid Family. Phenylalanine, tyrosine, and tryptophan. Additional compounds that can originate from the common aromatic pathway include enterochelin, p-aminobenzoate, ubiquinone, menaquinone, and NAD.

6. Histidine. This amino acid originates as an offshoot of the purine pathway in that a portion of the histidine molecule is derived from the intact purine ring.

Glutamine and Glutathione Synthesis

The importance of glutamate as one of the primary amino acids involved in the assimilation of ammonia is N2 Cycle. Glutamate and glutamine play acentral role in amino acid biosynthesis by the ready transfer of amino or amide groups, respectively, in the synthesis of other amino acids by transamination or transamidation reactions. Glutamine is synthesized from glutamate with the participation of ammonia and ATP. Glutathione, a disulfide-containing amino acid whose functions have only recently begun to be understood in detail, is synthesized in two steps. The coupling of L-glutamate and L-cysteine in the presence of ATP to form γ –glutamylcysteine is catalyzed by a specific synthase. In the presence of glycine and ATP, glutathione synthase forms glutathione.

Fig.Pathways from glutamate to glutamine, glutathione, proline, ornithine, and ALA.

The Proline Pathway

The pathway to proline involves formation of γ -glutamylphosphate from L-glutamate and ATP by γ -glutamyl kinase (ProB).

Aminolevulinate Synthesis

In S. enterica and E. coli, δ-aminolevulinic acid (ALA), the first committed precursor to tetrapyrroles, arises from glutamate. This C5 pathway, which was originally thought to occur primarily in plants and algae, is now firmly established as a major route to ALA in several bacterial species. Prior to this discovery, the condensation of glycine and succinyl-CoA by the enzyme ALA synthase (the C4 pathway) was considered to be the only route of ALA formation. It is still the major route of ALA formation in mammals, fungi, and certain bacteria, such as Rhodopseudomonas sphaeroides, R. capsulatus, and Bradyrhizobium japonicum. The C5 pathway to ALA involves conversion of glutamate to glutamyl-tRNAGlu by glutamyl-tRNA synthetase, reduction to glutamate γ -semialdehyde (GSA) by an NADPH-dependent glutamyl-tRNA reductase (HemA), and transamination by glutamate γ -semialdehyde aminomutase (HemL) to form ALA.

The Arginine Pathway

Bacteria and fungi synthesize ornithine via a series of N-acetyl derivatives. The function of the N-acetyl group is to prevent the premature cyclization of 1-pyrroline-5-carboxylate to proline. There is a divergence in the pathway in differentorganisms depending on the manner in which the acetyl group is removed. In Enterobacteriaceae and Bacillaceae, N-acetylornithine is deacylated via acetylornithine deacetylase (ArgE). In N. gonorrhoeae, Pseudomonadaceae, cyanobacteria, photosynthetic bacteria, and yeasts and molds, the acetyl group of N-acetylornithine is recycled by ornithine acetyltransferase (ArgJ).

Fig. Pathway of arginine biosynthesis.

Carbamoyl phosphate is a common precursor in the biosynthesis of arginine and pyrimidines. In E. coli and S. enterica a single carbamoyl phosphate synthetase catalyzes the reaction

Ammonia can replace glutamine as a nitrogen donor in vitro, but glutamine is the  physiologically preferred substrate, and K+ and Mg2+ are required participants.

Arginine degradation in E. coli, K. pneumoniae, and P. aeruginosa may follow yet another catabolic pathway: the arginine succinyltransferase (AST) pathway. In E. coli the enzymes in this pathway are encoded by genes in the astCADBE operon representing the structural genes for arginine succinyltransferase, succinylarginine dihydrolase, succinylornithine transaminase, succinylglutamic semialdehyde dehydrogenase, and succinylglutamate desuccinylase.

Fig. Arginine catabolic pathways

Disruption of any of the genes in this pathway prevents arginine catabolism and impairs ornithine utilization. In P. aeruginosa these same genes are designated aru (for arginine utilization). Arginine metabolism is of considerable significance in P. aeruginosa as evidenced by the strong chemotactic activity for this amino acid and the fact that there are four different catabolic pathways for arginine utilization: arginine deiminase, arginine succinyltransferase (AST), arginine dehydrogenase, and arginine decarboxylase. In S. cerevisiae, N. crassa, and in mammalian cells, arginine is degraded via the arginase pathway. In fungi, the arginine catabolic enzymes arginase (encoded by CAR1)and ornithine transaminase (encoded by CAR1) work in tandem to degrade arginine.