Biosynthesis of Amino Acids:- Chorismate Is a Key Intermediate in the Synthesis of Tryptophan, Phenylalanine, and Tyrosine
Aromatic rings are not readily available in the environ ment, even though the benzene ring is very stable. The branched pathway to tryptophan, phenylalanine, and tyrosine, occurring in bacteria, fungi, and plants, is the main biological route of aromatic ring formation. It proceeds through ring closure of an aliphatic precursor followed by stepwise addition of double bonds. The first four steps produce shikimate, a seven-carbon molecule derived from erythrose 4-phosphate and phospho enolpyruvate . Shikimate is converted to chorismate in three steps that include the addition of three more carbons from another molecule of phospho enolpyruvate. Chorismate is the first branch point of the pathway, with one branch leading to tryptophan, the other to phenylalanine and tyrosine.
In the tryptophan branch (Fig. 1), chorismate is converted to anthranilate in a reaction in which glutamine donates the nitrogen that will become part of the indole ring. Anthranilate then condenses with PRPP. The indole ring of tryptophan is derived from the ring carbons and amino group of anthranilate plus two car bons derived from PRPP. The final reaction in the sequence is catalyzed by tryptophan synthase. This en zyme has an α2β2 subunit structure and can be dissociated into two α subunits and a β2 subunit that catalyze different parts of the overall reaction:
Indole-3-glycerol phosphate → indole + glyceraldehyde 3-phosphate
Indole + serine → tryptophan+H2O
FIGURE 1 Biosynthesis of tryptophan from chorismate in bacteria and plants. In E. coli, enzymes catalyzing steps 1 and 2 are subunits of a single complex.
The second part of the reaction requires pyridoxal phosphate (Fig. 2). Indole formed in the first part is not released by the enzyme, but instead moves through a channel from the -subunit active site to the -subunit active site, where it condenses with a Schiff base inter mediate derived from serine and PLP. Intermediate channeling of this type may be a feature of the entire pathway from chorismate to tryptophan. Enzyme active sites catalyzing different steps (sometimes not sequential steps) of the pathway to tryptophan are found on single polypeptides in some species of fungi and bacteria, but are separate proteins in others. In addition, the activity of some of these enzymes requires a noncovalent association with other enzymes of the pathway. These observations suggest that all the pathway en zymes are components of a large, multienzyme complex in both prokaryotes and eukaryotes. Such complexes are generally not preserved intact when the enzymes are isolated using traditional biochemical methods, but evidence for the existence of multienzyme complexes is accumulating for this and a number of other metabolic pathways.
FIGURE 3 Biosynthesis of phenylalanine and tyrosine from chorismate in bacteria and plants. Conversion of chorismate to prephenate is a rare biological example of a Claisen rearrangement.
In plants and bacteria, phenylalanine and tyro sine are synthesized from chorismate in pathways much less complex than the tryptophan pathway. The common intermediate is prephenate (Fig. 3). The final step in both cases is transamination with glutamate. Animals can produce tyrosine directly from phenyl alanine through hydroxylation at C-4 of the phenyl group by phenylalanine hydroxylase; this enzyme also participates in the degradation of phenylalanine Tyrosine is considered a conditionally essential amino acid, or as nonessential insofar as it can be synthesized from the essential amino acid phenylalanine.
