# Structural Biochemistry/Enzyme/Allosteric Enzymes

Allosteric enzymes are an exception to the Michaelis-Menten model. Because they have more than two subunits and active sites, they do not obey the Michaelis-Menten kinetics but instead have sigmoidal kinetics.Since allosteric enzymes are cooperative, a sigmoidal plot of V$_0$ versus [S] results:
A sigmoidal plot has an S curve resulting from the combination of the T state and R state curves. The T state curve would be lower than the curve shown here, and the R state curve would be higher. Unlike many enzymes, allosteric enzymes do not obey Michaelis-Menten kinetics. The reason for this is that allosteric enzymes must account for multiple active sites and multiple subunits. Thus, allosteric enzymes show the sigmoidal curve shown above. The plot for reaction velocity, vo, versus the substrate concentration does not exhibit the hyperbolic plot predicted using the Michaelis-Menten equation. With allosteric enzymes, the catalytic activity affecting one substrate can alter the properties of other active sites located within the same enzyme. The result of this interaction equilibrium is a cooperative effect, meaning the binding of the substrate to an enzyme's active site affects the binding of substrate to other active sites. This property of cooperativity accounts for the sigmoidal curve of V$_0$ versus the concentration of substrate.
A. Introduction
Allosteric enzymes are unique compared to other enzymes because of its ability to adapt various conditions in the environment due to its special properties. The special property of Allosteric enzymes is that it contains an allosteric site on top of its active site which binds the substrate. The binding of a nonsubstrate molecule to the allosteric site functions to influences the activity of the enzyme. In influencing the activity, it can either enhance or impair the activity of the enzyme. Another important property of allosteric enzymes is that it also contains many polypeptide chains with multiple active and allosteric sites. The nonsubstrate molecules that bind at the allosteric sites are called allosteric modulators.
Example:
A clear example of an allosteric enzyme is aspartate trascarbamoylase. The enzyme catalyzes the first step in the synthesis of pyrimidines. The enzyme functions to catalyze the condensation of aspartate and carbamoyl phosphate to form Ncarbamoylaspartate and orthophosphate. The enzyme ultimately catalyzes the reaction that will yield cytidine triphosphate (CTP). This allosteric enzyme is unique in that for high products of the final product CTP, the enzyme activity is low. However, for low concentrations of the final product CTP, the enzymatic activity is high. The allosteric nature is thus represented as the CTP molecule has a odd configuration or shape that is unlike the substrates. Rather than binding to the active site, CTP binds to the allosteric site. Thus, CTP functions as an allosteric inhibitor decreasing the enzymatic activity of the enzyme. This enzyme also has separate regulatory and catalytic subunits on separate polypeptide chains. There are instances though when CTP concentrations remain high and cells in the body need more enzyme. This is when a different allosteric molecule ATP functions to attach to the allosteric site and functions as enzyme activator enhancing the activity of the enzyme. Thus, even with high concentrations of CTP, the enzyme activity could be enhanced because of ATP, which also acts on the allosteric site. This example explains the benefits of allosteric control and the ability allosteric enzymes to adapt to various conditions of the environment. This is particularly helpful for cells because there are occasions when the cell requires an allosteric activator like "ATP" to enhance the enzyme even when it is inhibited due to high amounts of product. (CTP) The aspect of feedback inhibition is represented as well as high amounts of product acts to inhibit the action of the enzyme acting in a inhibitory manner.
B. Properties of Allosteric Enzymes
There are distinct properties of Allosteric Enzymes that makes it different compared to other enzymes.
(1) One is that allosteric enzymes do not follow the Michaelis-Menten Kinetics. This is because allosteric enzymes have multiple active sites. These multiple active sites exhibit the property of cooperativity, where the binding of one active site affects the affinity of other active sites on the enzyme. As mentioned earlier, it is these other affected active sites that result in a sigmoidal curve for allosteric enzymes.
(2) Allosteric Enzymes are influenced by substrate concentration. For example, at high concentrations of substrate, more enzymes are found in the R state. The T state is favorite when there is an insufficient amount of substrate to bind to the enzyme. In other words, the T and R state equilibrium depends on the concentration of the substrate.
(3) Allosteric Enzymes are regulated by other molecules. This is seen when the molecules 2,3-BPG, pH, and CO2 modulates the binding affinity of hemoglobin to oxygen. 2,3-BPG reduces binding affinity of O2 to hemoglobin by stabilizing the T- state. Lowering the pH from physiological pH=7.4 to 7.2 (pH in the muscles and tissues)favors the release of O2. Hemoglobin is more likely to release oxygen in CO2 rich areas in the body.
References
Biochemistry 6th edition. Berg, Jeremy M; Tymoczko, John L; Stryer, Lubert. W.H. Freeman Company, New York