L-Arogenate

Figure 1. Hypothetical mechanism for shuttling of intermediates of the common aromatic pathway between plastidic and cytosolic compartments. Enzymes denoted with an asterisk (DAHP synthase-Co, chorismate mutase-2, and cytosolic anthranilate synthase) have been demonstrated to be isozymes located in the cytosol. DAHP molecules from the cytosol are shown to be shuttled into the plastid compartment in exchange for EPSP molecules synthesized within the plastid. Abbreviations C3, phosphoenolpyruvate C4, erythrose 4-P DAHP, 3-deoxy-D-arabino-heptulosonate 7-phosphate EPSP, 5-enolpyruvylshikimate 3-phosphate CHA, chorismate ANT, anthranilate TRP, L-tryptophan PPA, prephenate AGN, L-arogenate TYR, L-tyrosine and PHE, L-phenylalanine.

L-Pratyrosine [L-arogenic acid, (5)-cis-a-amino-l-carboxy-4-hydroxy-2,5-cyclohexadiene-1 -propanoic acid]. 

Figure 2 illustrates the recent observation that tyrosine may be formed from either L-arogenate or from 4-hydroxyphenylpyruvate, while phenylalanine may be formed from either L-arogenate or from phenylpyruvate. Some organisms fail to use L-arogenate for aromatic biosynthesis... 

Fig. 2. Flow routes to phenylalanine and tyrosine in nature. Abbreviations CHA, chorismate PPA, prephenate HPP, 4-hydroxyphenylpyruvate AGN, L-arogenate PPY, phenylpyruvate TYR, L-tyrosine PHE, L-phenylalanine.

DAHP synthase-Co was insensitive to allosteric effects of aromatic-pathway compounds, although caffeic acid was inhibitory. On the other hand, DAHP synthase-Mn was found to be sensitive to feedback inhibition by L-arogenate in both mung bean and in N. silvestris. In mung bean, where the most detailed studies have been done thus far, a number of other pathway intermediates produced allosteric effects. 

Fig. 4. HPLC assay for L-phenylalanine produced as the result of the reaction catalyzed by arogenate dehydratase. The reaction mixture contained 1 ir L-arogenate, 0.5 nM L-tyrosine and enzyme purified about 3-fold by precipitation with NHi+SOi at 40% of saturation. Reaction time was 30 min at 33 C.

Fig. 9. Sequential pattern of allosteric control over biosynthesis of aromatic amino acids in the plastid compartment. In the presence of excess aromatic amino acids, L-tyrosine (TYR) inhibits arogenate dehydrogenase, L-phenylalanine (PHE) inhibits arogenate dehydratase and L-tryptophan (TRP) inhibits anthranilate synthase. The three aromatic amino acids exert allosteric inhibition (-) or activation (+) effects upon chorismate mutase-1 as symbolized. However, activation dominates over inhibition. The outcome of these events is to trap L-arogenate (AGN) between the various foci of control in the pathway. As shown symbolically, -arogenate (AGN) then acts to feedback inhibit DAHP synthase-Mn.

The aromatic amino acid pathway branches at L-arogenate in Euglena gracilis. Mol. Cell Biol. 1 426-438. 

L-Tyrosine biosynthesis starts with the condensation of phosphoenolpyruvate (PEP) and erythrose-4-phosphate (E4P), the intermediates of the glycolytic pathway and pentose phosphate pathway, respectively, which is catalyzed by 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHPS aroE/aroG/aroH). The resultant 3-deoxy-D-arabino-heptulosonate (DAHP) is converted into chorismate through the shikimate pathway with seven reactions. In plants, prephenate (PPA) is converted into L-arogenate by transamination whereas in E. coli, PPA is converted to p-hydroxyphenylpyruvate (HPP) by prephenate dehydrogenase, which is a bifunctional enzyme that behaves as chorismate mutase/prephenate... 

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