Nonallosteric enzymes

Figure 2.12 Graphical representation of the Michaelis-Menten equation for nonallosteric enzymes.

The Michaelis-Menten model is commonly employed in describing nonallosteric enzyme reactions. The overall model can be pictured as follows (Equation 16.25) where E represents the enzyme, M the reacting molecule(s), E + M EM is associated with ki and the reverse reaction associated with k i and EM E + P is associated with 2-... 

Allosteric enzymes are generally larger and more complex than nonallosteric enzymes. Most have two or more subunits. Aspartate transcarbamoylase, which catalyzes an early reaction in the biosynthesis of pyrimidine nucleotides (see Fig. 22-36), has 12 polypeptide chains organized into catalytic and regulatory subunits. Figure 6-27 shows the quaternary structure of this enzyme, deduced from x-ray analysis. 

Specific small molecules or ions can inhibit even nonallosteric enzymes. In irreversible inhibition, the inhibitor is covalently linked to the enzyme or bound so tightly that its dissociation from the enzyme is very slow. Covalent inhibitors provide a means of mapping the enzyme s active site. In contrast, reversible inhibition is characterized by a rapid equilibrium between enzyme and inhibitor. A competitive inhibitor prevents the substrate from binding to the active site. It reduces the reaction velocity by diminishing the proportion of enzyme molecules that are bound to substrate. In noncompetitive inhibition, the inhibitor decreases the turnover number. Competitive inhibition can be distinguished from noncompetitive inhibition by determining whether the inhibition can be overcome by raising the substrate concentration. 

The reaction rate is directly proportional to the concentration of the enzyme if an excess of free substrate molecules is present. Thus, enzyme-substrate interactions obey the mass-action law. For a given enzyme concentration, the reaction velocity increases initially with increasing substrate concentration. Eventually, a maximum is reached, and further addition of substrate has no effect on reaction velocity (v) (Figure 6-4). The shape of a plot of V versus [S] is a rectangular hyperbola and is characteristic of all nonallosteric enzymes (Chapter 7). At low substrate concentrations, the reaction rate is proportional to substrate concentration, with the reaction following first-order kinetics in terms of substrate concentration. 

The difference between the velocity curves for chymotrypsin and aspartate transcarbamoylase demonstrates the difference between an allosteric enzyme and a nonallosteric enzyme. 

A particularly useful model for the kinetics of enzyme-catalyzed reactions was devised in 1913 by Leonor Michaelis and Maud Menten. It is stiU the basic model for nonallosteric enzymes and is widely used, even though it has undergone many modifications. 

Michaelis and Menten developed a series of mathematical relationships to explain the behavior of many nonallosteric enzymes. 

Why do chymotrypsin and ATCase have different velocity curves Chymotrypsin and aspartate transcar-bamoylase exhibit different types of kinetics. Chymotrypsin is a nonallosteric enzyme and exhibits hyperbolic kinetics. ATCase is an allosteric enzyme. It has multiple subunits, and the binding of one molecule of substrate affects the binding of the next molecule of substrate. It exhibits sigmoidal kinetics. 

When ATGase catalyzes the condensation of aspartate and carbamoyl phosphate to form carbamoyl aspartate, the graphical representation of the rate as a function of increasing substrate concentration (aspartate) is a sigmoidal curve rather than the hyperbola obtained with nonallosteric enzymes (Figure 7.2a). The sigmoidal curve indicates the cooperative behavior of allosteric enzymes. In this two-substrate reaction, aspartate is the substrate for which the concentration is varied, while the concentration of carbamoyl phosphate is kept constant at high levels. 

Even though it is tempting to consider inhibition of allosteric enzymes in the same fashion as nonallosteric enzymes, much of the terminology is not appropriate. Competitive inhibition and noncompetitive inhibition are terms reserved for the enzymes that behave in line with Michaelis-Menten kinetics. With allosteric enzymes, the situation is more complex. In general, two types of enzyme systems exist, called K systems and V systems. A K system is an enzyme for which the substrate concentration that yields one-half is altered by the presence... 

Allosteric enzymes exhibit different behaviors compared to nonallosteric enzymes, and the Michaelis-Menten equations are not applicable. 

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