Metabolism of Aromatic Amino Acids and Histidine

The biosynthesis of heterocyclic and/or aromatic rings from noncyclic precursors requires complex chemical reactions. Most of these reactions (except the hydroxylation of phenylalanine to tyrosine) have been lost through evolution in animal metabolism.

Figure 21.12 provides an overview of the biosynthesis of aromatic amino acids and histidine. Note that the aromatic amino acids are involved in pathways for the synthesis of lignin (a major constituent of woody tissue) and auxins (a class of plant hormones).

Note also that a key intermediate in the synthesis of virtually all aromatic compounds in the cells is shikimic acid. These include phenylalanine, tyrosine, tryptophan, p-aminobenzoic acid, and p-hydroxybenzoic acid. The precursors to shikimic acid, however, are erythrose-4-phosphate and phosphoenolpyruvate (Figure 21.13). In fact, all of the carbons in phenylalanine and tyrosine are derived from these two compounds.

Besides showing the unbranched pathway from erythrose-4-phosphate and phosphoenolpyruvate to shikimic acid, Figure 21.13 also shows the sequence of reactions from shikimic acid to chorismate, the first major branch point in the synthesis of the aromatic amino acids and histidine. The sixth reaction of the shikimic acid pathway is inhibited specifically by glyphosate (see here), which is the active ingredient in the broad spectrum herbicide known as Roundup.

Diverging pathways from chorismate to the five aromatic compounds above are shown schematically in Figure 21.12 and in detail in Figure 21.14. The structure of the last enzyme in the synthesis of tryptophan, tryptophan synthase, consists of an 2 2 dimer in which the separate subunits apparently catalyze the reactions (see here) in the enzyme and actually transfers the indol product through a tunnel in the interior part of the molecule. A schematic depiction of the tryptophan synthase reactions is shown in Figure 21.16.

See also: Biosynthesis of Histidine / Ames Test, Aromatic Amino Acid Utilization

INTERNET LINKS:

> 1. Phenylalanine, Tyrosine, and Tryptophan Biosynthesis

> 2. Tyrosine Metabolism

> 3. Phenylalanine Metabolism

> 4. Tryptophan Metabolism

> 5. Histidine Metabolism