Allosteric control effects

Nitrogen is normally supplied as an ammonium compound in dtric acid fermentations and suffident has to be supplied to enable the effect of manganese deficiency (increased levels of ammonium in the metabolic pool) to occur. Remember that increased metabolic pool ammonium has the effect of releasing the allosteric controls exerted on phosphofructokinase. 

The first phosphatase step is very important FBPase converts fructose,1-6-bisphos-phate into fructose-6-phosphate under allosteric control of several factors but during fasting, glucagon-induced regulation is crucial. One effect of glucagon stimulation of liver cells is to reduce the concentration of fructose-2,6-bisphosphate, an isomer that activates PFK-1 and is itself synthesized by PFK-2 when fructose-6-phosphate concentration rises... 

A system such as this can provide a powerful mechanism for transcriptional control. While bound to nucleosomes, PARP-1 promotes a transcriptionally repressed state, but one that is simultaneously poised for activation because of the allosteric activating effect of nucleosomes on PARP-1 enzymatic activity. In the presence of NAD+, PARP-1 can autoPARylate and release from nucleosomes, shifting the chromatin to a more transcriptionally active conformation. PARC can reset the system by cleaving the PAR chains from PARP-1, allowing PARP-1 to re-bind the nucleosomes and re-establish a transcriptionally repressed state. 

What is the minimum size of synzymes And is there any control effect observed that is analogous to the allosteric control of enzyme activities ... 

To limit futile cycling between glycolysis and gluconeogenesis, the two pathways are under reciprocal allosteric control, mainly achieved by the opposite effects of fructose 2,6-bisphosphate on PFK-1 and FBPase-1. 

Allosteric regulation can be considerably more complex. An example is the remarkable set of allosteric controls exerted on glutamine synthetase of E. coli (Fig. 22-6). Six products derived from glutamine serve as negative feedback modulators of the enzyme, and the overall effects of these and other modulators are more than additive. Such regulation is called concerted inhibition. 

In allosteric enzymes, the activity of the enzyme is modulated by a non-covalently bound metabolite at a site on a protein other than the catalytic site. Normally, this results in a conformational change, which makes the catalytic site inactive or less active. Covalent modulated enzymes are interconverted between active and inactive forms by the action of other enzymes, some of which are modulated by allosteric-type control. Both of these control mechanisms are responsive to changes in cell conditions and typically the response time in allosteric control is a matter of seconds as compared with minutes in covalent modulation. A third type of control, the control of enzyme synthesis at the transcription stage of protein synthesis (see Appendix 5.6), can take several hours to take effect. 

Uglem, G. L., Dupre, R. K. Harley, J. P. (1983). Allosteric control of pyrimidine transport in Hymenolepis diminuta an unusual kinetic isotope effect. Parasitology, 87 289-93. 

The hemoglobin family of macromolecules exhibits virtually all the important features of protein structure, function, and evolution, principles of protein folding, subunit movement and allosteric control in regulating activity, effects of point mutations on molecular behavior, and gene structure and genetic control. 

How does an organism ensure that glycogen synthesis and glycogen breakdown do not operate simultaneously If this were to occur, the main result would be the hydrolysis of UTP, which would waste chemical energy stored in the phosphoric anhydride bonds. A major controlling factor lies in the behavior of glycogen phosphorylase. This enzyme is subject not only to allosteric control but also to another control feature covalent modification. We saw an earlier example of this kind of control in the sodium-potassium pump in Section 8.6. In that example, phosphorylation and dephosphorylation of an enzyme determined whether it was active, and a similar effect takes place here. 

There is kinetic evidence (66-67) that the target of allosteric effectors is CPS.B. Since the CPS subdomains are functionally and structurally equivalent, we were curious as to whether CPS.A could be placed under allosteric control. To determine whether this occurs, a second chimeric molecule (R2) was constructed (21) in which the mammalian regulatory domain (B3) replaced the A3 subdomain in E. coli CPS.A (Figure 11). The control mechanisms (Figure 12) are nearly the same as that observed for the mammalian CAD. The chimera is inhibited by UTP and activated by PRPP although the affinity for the latter ligand is somewhat lower than in the native molecule. While chimera R1 was catalytically active, its aggregation made it a poor substrate for protein kinase A. The second chimera, R2 is monodisperse and can be readily phosphorylated. Protein kinase A abolishes UTP inhibition and reduces the affinity of the protein for PRPP, the same effect observed in CAD. 

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.

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