The first chemical reaction common to the synthesis of tryptophan, tyrosine, and phenylalanine is the condensation of erythrose-4-P and phosphoenolpyruvate to form 3-deoxy-D-arabino-heptulosonate-7-P, DAHP, a reaction catalyzed by DAHP synthetase (Fig. 1). Due to its position at the head of the aromatic amino acid biosynthetic pathway and to the fact that this reaction is irreversible, it is logical that this reaction should be a key point of regulation. Indeed, this expectation is met. Escherichia coli regulates both the amount and activity per molecule of DAHP synthetase as a function of the intracellular levels of the aromatic amino acids.

Fig1. Outline of the aromatic amino acid biosynthetic pathway in Escherichia coli. Each arrow represents an enzymatic step. Tryptophan feedback inhibits one of the DAHP synthetases, AroH, as well as the first enzyme of the pathway committed to tryptophan synthesis.

A double regulation of total DAHP synthetase activity is logical. While regulation of the enzyme level minimizes unnecessary consumption of amino acids and energy in the synthesis of the enzyme, this type of regulation is incapable of producing appreciable changes in the enzyme levels or of total enzyme activity on time scales shorter than minutes. A much more rapidly-responding regulation mechanism is also necessary to adjust the synthesis rates of tryptophan, tyrosine, and phenylalanine on time scales of seconds.

In addition to stabilizing the activity of the synthetic pathway against random fluctuations, a rapidly responding regulation would fine-tune the biosynthetic flow rates of the aromatic amino acids and would be able to respond rapidly to growth rate changes generated by changes in the nutrient medium. Feedback inhibition of an enzyme’s activity meets the requirements, as this mechanism can alter an enzyme’s activity in milliseconds.

Feedback inhibition is an example of an allosteric interaction in which accumulation of the product of the pathway leads to inhibition of the activity of an enzyme in that pathway. This is a specific example of an allosteric interaction in which a molecule dissimilar in shape to the substrates of an enzyme can bind to the enzyme, usually at a site on the enzyme far from the active site, and can generate conformational changes that alter the catalytic activity of the enzyme. Feedback inhibition can reduce an enzyme’s activity in either of two fundamental ways (Fig. 2). The tryptophan-sensitive DAHP synthetase is feedback-inhibited largely as a result of a change in its V_max, whereas the first enzyme of the pathway used solely for tryptophan synthesis, anthranilate synthetase, is an example of the other possibility. It is feedback inhibited by tryptophan via a change in its K_m.

Fig2. Two possibilities for feedback inhibition of an enzyme. The top curve is enzyme velocity as a function of substrate concentration, and the equation is the activity of an uninhibited enzyme as a function of its K_m, V_max, and substrate concentration S.

Bacillus subtilus possesses a single DAHP synthetase whose synthesis and activity is regulated by the three aromatic amino acids. Escherichia coli, however, possesses three different DAHP synthetases. The activity of one, the AroH protein, is feedback-inhibited by tryptophan, another is feedback-inhibited by tyrosine, and the third is feedback-inhibited by phenylalanine. Only if the cell’s growth medium possesses all three amino acids is all DAHP synthetase activity within an E. coli cell fully inhibited.

This is an example of the fact that different microorganisms possess different overall schemes for the regulation of tryptophan synthesis. On one hand, it is possible that the different evolutionary niches occupied by different microorganisms require these different schemes. On the other hand, perhaps one scheme is no better than another, and the different ones just happened to have evolved that way. Either way, this diversity means that the overall scheme for regulation of tryptophan synthesis in E. coli is not the only one that works.

اخر الاخبار

اخبار العتبة العباسية المقدسة

خمسون عامًا من العطاء.. نجم الأعرجي خادم الزائرين بلا انقطاع

العتبة العباسية المقدسة تواصل إقامة مجالسها العزائية لإحياء شهر المحرم

العتبة العباسية المقدسة تطلق سلسلة محاضرات قرآنية عاشورائية في بابل

في مساء اليوم الخامس من المحرّم.. المواكب الكربلائيّة تواصل فعالياتها العزائية

المزيد

الآخبار الصحية

لهذا السبب.. إغلاق 25 مركزًا لعلاج الإدمان في مصر ؟

خلافا للاعتقاد الشائع.. علماء يكشفون أسرار بذور البطيخ ؟!

هذا ما يحدث لجسمك عند تناولك الطماطم بانتظام !

تعرف على أطعمة تسرّع "تعافي الجسم" من حروق الشمس

المزيد

الآخبار التكنلوجية

الثلوج تغطي الصحراء الأكثر جفافا في العالم!

بتلسكوب "ألما".. التقاط صورا غير مسبوقة لبدايات الكون !

هل هاتفك مراقب؟.. 5 علامات خطيرة تكشف التجسس عليك

دبي تطلق أول رحلة تجريبية للتاكسي الجوي

المزيد

مواضيع ذات صلة

Early Explorations of the Hypersynthesis

The Serendipitous Discovery of trp Enzyme Hypersynthesis

Rapid Induction Capabilities of the trp Operon

How AraC Protein Loops and Unloops

DNA Looping and Repression of araBAD

Binding Sites of the ara Regulatory Proteins

Endoplasmic Reticulum-Associated Degradation and the Unfolded Protein Response

Protein Folding and Modifications in the Endoplasmic Reticulum

Protein Modifications

Regulating AraC Synthesis

Repression by AraC

Detection and Isolation of AraC Protein