Tryptophan feedback inhibition

The availability of tryptophan is also a determining factor in the formation of indoleacetic acid the pool size of tryptophan is regulated in part by tryptophan feedback inhibition of anthranilate synthase. 

A Try mutant would not be subject to feedback inhibition by overproduction of tryptophan. Also, the mutation may allow more chorismate to proceed to prephenate via E3 (see Figure 8.4) and thus through to L-phenylalanine. 

Most bacteria and fungi have three isozymes of DAHP synthase, each controlled by feedback inhibition by one of the three products tyrosine, phenylalanine, or tryptophan. In E. coli these are encoded by genes aro F, am G, and aro H, respectively.11-123 All of the enzymes contain one atom of iron per molecule and show spectral similarities to hemerythrin.13... 

Molecules with structures as diverse as carbamoyl-phosphate, tryptophan, and cytidine triphosphate are feedback inhibitors of the E. coli glutamine synthase. The feedback inhibition is cumulative, with each metabolite exerting a partial inhibition on the enzyme. Why would complete inhibition of the glutamine synthase by a single metabolite be metaboli-cally unsound ... 

By use of synthetic medium the formation of 3,4-trans-CH D was maintained for a 36-h cultivation period, resulting in accumulation of up to 790 mg L 1 3,4-trans-CHD 1 [11]. With this strain, however, it is necessary to separate the growth and production phases, because the substances for which E. coli strain BN117 is known to be auxotrophic, i.e. tryptophan, tyrosine, phenylalanine, proline, arginine, histidine, and p-aminobenzoate, also partially inhibit entry to the chorismate biosynthesis pathway (feedback inhibition of DAHP-synthase). 

Fig. 2 Metabolic pathways in C. glutamicum for biosynthesis of the aromatic amino acids tryptophan, tyrosine, and phenylalanine (a) and amino acids belonging to the aspartate family including lysine, methionine, threonine, and isoleucine (b). Metabolic regulation by feedback inhibition is indicated by dotted lines...

Tryptophan dioxygenase has a short half-life (of the order of 2 hours) and is subject to regulation by three mechanisms saturation with its heme cofactor, hormonal induction and feedback inhibition, and repression by NAD(P). 

Cumulative feedback Inhibition - Eight specific feedback inhibitors, which are either metabolic end products of glutamine (tryptophan, histidine, glucosamine-6-phosphate, carbamoyl phosphate, CTP, or AMP) or indicators of the general status of amino acid metabolism (alanine or glycine), can bind to any of the subunits of the enzyme and at least partially inhibit it. The more inhibitors that bind, the greater the inhibition. 

Cumulative feedback Inhibition - Eight specific feedback inhibitors, which are either metabolic end products of glutamine (tryptophan, histidine, glucosamine-6-phosphate, carbamoyl phosphate, CTP, or... 

Similarly, enzymes can be allosterically regulated by association with other molecules. Often the first enzyme in a metabolic pathway is feedback-inhibited by the product of that pathway. For example, anthranilate synthetase, the first enzyme in the biosynthesis of tryptophan, is inhibited by tryptophan, but not by other amino acids. 

In B. subtilis, the pathway from chorismate to tryptophan is feedback-inhibited by tryptophan, which suppresses anthranilate synthase activity. Mutant B. subtilis that lacks tryptophan synthetase can grow on minimal medium only when supplemented with exogenous tryptophan. Under these conditions, none of the intermediates in the tryptophan biosynthetic pathway from anthranilate to indole 3-glycerol phosphate are produced. However, when the bacteria have depleted the medium of tryptophan, the levels of those intermediates increase, even though there is no net production of tryptophan. Why ... 

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