Regulation allosteric

ACTase catalyzes the transfer of a carbamoyl residue from carbamoyl phosphate to the amino group of L-aspartate. The N-carbamoyl L-aspartate formed in this way already contains all of the atoms of the later pyrimidine ring (see p. 188). The ACTase of the bacterium Escherichia coli is inhibited by cytidine triphosphate (CTP), an end product of the anabolic metabolism of pyrimidines, and is activated by the precursor ATP. 

In contrast to the kinetics of isosteric (normal) enzymes, allosteric enzymes such as ACTase have sigmoidal (S-shaped) substrate saturation curves (see p. 92). In allosteric systems, the enzyme s af nity to the substrate is not constant, but depends on the substrate concentration [A]. Instead of the Michaelis constant Km (see p. 92), the substrate concentration at half-maximal rate ([AJo.s) is given. The sigmoidal character of the curve is described by the Hill coef cient h. In isosteric systems, h = 1, and h increases with increasing sigmoid icity. 

Depending on the enzyme, allosteric effectors can influence the maximum rate V ax. the semi-saturation concentration [A]o.5, and the Hill coef dent h. If it is mainly V ax that is changed, the term V system is used. Much more common are K systems , in which allosteric effects only influence [A]o.5 and h. 

The K type also includes ACTase. The inhibitor CTP in this case leads to right-shifting of the curve, with an increase in [A]o.5 and h (curve II). By contrast, the activator ATP 

The subunits of ACTase each consist of two domains—i.e., independently folded partial structures. The N-terminal domain of the regulatory subunit (right) mediates interaction with CTP or ATP (green). A second, Zn -con-taining domain (Zn shown in light blue) establishes contact with the neighboring catalytic subunit. Between the two domains of the catalytic subunit lies the active center, which is occupied here by two substrate analogs (red). 

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Perutz, M. Mechanisms of cooperativity and allosteric regulation in proteins. Cambridge Cambridge University Press, 1990. 

Allosteric regulation acts to modulate enzymes situated at key steps in metabolic pathways. Consider as an illustration the following pathway, where A is the precursor for formation of an end product, F, in a sequence of five enzyme-catalyzed reactions ... 

Glycogen Phosphorylase Allosteric Regulation and Covalent Modification 473... 

In the Monod-Wyman-Changeux model for allosteric regulation, what values of L and relative affinities of R and T for A will lead activator A to exhibit positive homotropic effects (That is, under what conditions will the binding of A enhance further A-binding, in the same manner that S-binding shows positive coop-... 

Metabolic regulation is achieved via regulating enzyme activity in three prominent ways allosteric regulation, covalent modi-... 

The hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate (Eigure 23.7), like all phosphate ester hydrolyses, is a thermodynamically favorable (exergonic) reaction under standard-state conditions (AG° = —16.7 kj/mol). Under physiological conditions in the liver, the reaction is also exergonic (AG = —8.6 kJ/mol). Fructose-1,6-bisphosphatase is an allosterically regulated enzyme. Citrate stimulates bisphosphatase activity, hut fructose-2,6-bisphosphate is a potent allosteric inhibitor. / MP also inhibits the bisphosphatase the inhibition by / MP is enhanced by fructose-2,6-bisphosphate. 

Freire, E. (2000). Can allosteric regulation be predicted from structure Proc. Natl. Acad. Sci. U.S.A. 97 11680-11682. 

The influence of pH on the affinity of Hb for oxygen known as the Bohr-effect indicates that protons retain the allosteric regulation of oxygen transport. It is also an indirect confirmation of the ability of Hb and Im Hb for transporting carbon dioxide. The values of the Bohr-effect d log P50/d pH for Hb and Im Hb are close to each other in the pH range 7.1-7.4. It is possible that the effect of the micro-environment of carboxylic CP on immobilized Hb and its polyfunctional interaction represents the interaction between Hb and the structural elements inside the red cell [99]. 

This reaction is followed by another phosphorylation with ATP catalyzed by the enzyme phosphofructoki-nase (phosphofructokinase-1), forming fructose 1,6-bisphosphate. The phosphofructokinase reaction may be considered to be functionally irreversible under physiologic conditions it is both inducible and subject to allosteric regulation and has a major role in regulating the rate of glycolysis. Fructose 1,6-bisphosphate is cleaved by aldolase (fructose 1,6-bisphosphate aldolase) into two triose phosphates, glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Glyceraldehyde 3-phosphate and dihydroxyacetone phosphate are inter-converted by the enzyme phosphotriose isomerase. 

Changes in enzyme levels and allosteric regulation of carbamoyl phosphate synthase by A -acetylglutamate regulate urea biosynthesis. 

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