Erythrose 4-phosphate and Phosphoenolpyruvate Family
Regulation of the Aromatic Amino Acids
Phenylalanine, tyrosine, and tryptophan are known as the aromatic amino acids. The synthesis of all three share a common beginning to their pathways; the formation of chorismate from phosphoenolpyruvate (PEP) and erythrose 4- phosphate (E4P). The first step, condensation of 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP) from PEP/E4P, uses three isoenzymes AroF, AroG, and AroH. Each one of these has its synthesis regulated from tyrosine, phenylalanine, and tryptophan, respectively. These isoenzymes all have the ability to help regulate synthesis of DAHP by the method of feedback inhibition. This acts in the cell by monitoring the concentrations of each of the three aromatic amino acids. When there is too much of any one of them, that one will allosterically control the DAHP synthetase by “turning it off”. With the first step of the common pathway shut off, synthesis of the three amino acids can not proceed. The rest of the enzymes in the common pathway (conversion of DAHP to chorismate) appear to be synthesized constitutively, except for shikimate kinase which can be inhibited by shikimate through linear mixed-type inhibition. If too much shikimate has been produced then it can bind to shikimate kinase to stop further production.
Besides the regulations described above, each amino acids terminal pathway can be regulated. These terminal pathways progress from chorismate to the final end product, either tyrosine, phenylalanine, or tryptophan. Each one of these pathways is regulated in a similar fashion to the common pathway; with feedback inhibition on the first committed step of the pathway.
Tyrosine and phenylalanine share the same initial step in their terminal pathways, chorismate converted to prephenate which is converted to an amino acid-specific intermediate. This process is mediated by a phenylalanine (PheA) or tyrosine (TyrA) specific chorismate mutase-prephenate dehydrogenase. The reason for the amino acid-specific enzymes is because PheA uses a simple dehydrogenase to convert prephenate to phenylpyruvate, while TyrA uses a NAD-dependent dehydrogenase to make 4-hydroxylphenylpyruvate. Both PheA and TyrA are feedback inhibited by their respective amino acids. Tyrosine can also be inhibited at the transcriptional level by the TyrR repressor. TyrR binds to the TyrR boxes on the operon near the promoter of the gene that it wants to repress.
In the terminal-tryptophan synthesis pathway, the initial step converts chorismate to anthranilate using anthranilate synthase. This enzyme requires either ammonia or glutamine as the amino group donor. Anthranilate synthase is regulated by the gene products of trpE and trpD. trpE encodes the first subunit, which binds to chorismate and moves the amino group from the donor to chorismate. trpD encodes the second subunit, which is simply used to bind glutamine and use it as the amino group donor so that the amine group can transfer to the chorismate. Anthranilate synthase is also regulated by feedback inhibition. The finished product of tryptophan, once produced in great enough quantities, is able to act as the co-repressor to the TrpR repressor which represses expression of the trp operon.
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