Michaelis- Menten enzyme kinetics noncompetitive inhibition

The term should be used for enzymes that display Michaelis-Menten kinetics. Thus, it is not used with allosteric enzymes. Technically, competitive and noncompetitive inhibition are also terms that are restricted to Michaelis-Menten enzymes, although the concepts are applicable to any enzyme. An inhibitor that binds to an allosteric enzyme at the same site as the substrate is similar to a classical competitive inhibitor. One that binds at a different site is similar to a noncompetitive inhibitor, but the equations and the graphs characteristic of competitive and noncompetitive inhibition don t work the same way with an allosteric enzyme. 

For each of the four types of inhibition of a Michaelis-Menten enzyme [competitive, Eq. (5.25) noncompetitive and mixed Eq. (5.29) and uncompetitive, Eq. (5.32)], derive the corresponding Lineweaver-Burk equations [Eqs. (5.26), and (5.30), respectively] and draw the characteristic plots that are the basis for the rapid visnal identification of which type of inhibition apphes when analyzing enzyme kinetic data. 

Kinetic Model Reversible CYP inhibition is dependent on the mode of interaction between CYP enzymes and inhibitors and is further characterized as competitive, noncompetitive, uncompetitive, and mixed. Evaluation of reversible inhibition of CYP reactions is often conducted under conditions where Michaelis-Menten (MM) kinetics is obeyed. Based on Scheme 1 below, various types of reversible inhibition are described from the scheme during catalysis which can lead to enzyme inhibition ... 

El to E4 are irreversible enzymes that follow Michaelis-Menten kinetics. Ei and E2 are inhibited by the noncompetitive inhibitors li and I2. Concentrations of Xi are held constant. Inputs concentrations of E and E. Output steady-state concentration of A. The concentrations of the species marked with ( ) are fixed. 

Substances that cause enzyme-catalyzed reactions to proceed more slowly are termed inhibitors, and the phenomenon is termed inhibition. When an enzyme is subject to inhibition, the reaction still may obey Michaelis-Menten kinetics but with apparent Km and Vmax values that vary with the inhibitor concentration. If the inhibitor acts only on the apparent Km, it is a competitive inhibitor if it affects only the apparent Vmax, it is a noncompetitive inhibitor and if it affects both constants, it is an uncompetitive inhibitor. 

Competitive inhibition occurs, when substrate and inhibitor compete for binding at the same active site at the enzyme. Based on the Michaelis-Menten kinetics, Vmax is unchanged whereas Km increases. In case of noncompetive inhibition, the inhibitor and the substrate bind to different sites at the enzyme. Vmax decrease whereas the Km value is unaffected. Binding of the inhibitor only to the enzyme-substrate complex is described as uncompetitive inhibition. Both, Vmax and Km decrease. Finally, mixed (competitive-noncompetitive) inhibition occurs, either the inhibitor binds to the active or to another site on the enzyme, or the inhibitor binds to the active site but does not block the binding of the substrate. 

Michaelis-Menten kinetics and, depending on their preference of binding to the free enzyme and/or the enzyme-substrate complex, competitive, uncompetitive, and noncompetitive inhibition patterns can be distinguished. For the purposes of this discussion it will be assumed that the initial equilibrium of free and bound substrate is established significantly faster than the rate of the chemical transformation of substrate to product, that is,... 

How can we determine whether a reversible inhibitor acts by competitive or noncompetitive inhibition Let us consider only enzymes that exhibit Michaelis- Menten kinetics. Measurements of the rates of catalysis at different concentrations of substrate and inhibitor serve to distinguish the three types of inhibition. In competitive inhibition, the inhibitor competes with the substrate for the active site. The dissociation constant for the inhibitor is given by... 

In textbooks dealing with enzyme kinetics, it is customary to distinguish four types of reversible inhibitions (i) competitive (ii) noncompetitive (iii) uncompetitive and, (iv) mixed inhibition. Competitive inhibition, e.g., given by the product which retains an affinity for the active site, is very common. Non-competitive inhibition, however, is very rarely encountered, if at all. Uncompetitive inhibition, i.e. where the inhibitor binds to the enzyme-substrate complex but not to the free enzyme, occurs also quite often, as does the mixed inhibition, which is a combination of competitive and uncompetitive inhibitions. The simple Michaelis-Menten equation can still be used, but with a modified Ema, or i.e. ... 

The answer is c. (Murray, pp 48-73. Scriver, pp 4571-4636. Sack, pp 3-17. Wilson, pp 287-317.) Allosteric enzymes, unlike simpler enzymes, do not obey Michaelis-Menten kinetics. Often, one active site of an allosteric enzyme molecule can positively affect another active site in the same molecule. This leads to cooperativity and sigmoidal enzyme kinetics in a plot of [S] versus V The terms competitive inhibition and noncompetitive inhibition apply to Michaelis-Menten kinetics and not to allosteric enzymes. 

The inhibition of certain enzymes by specific metabolites is an important element in the regulation of intermediary metabolism and most often occurs with cooperative enzymes that are regulated allosterically. Inhibition of enzymes that obey the Michaelis-Menten equation, noncooperative enzymes, is more commonly used by pharmacists to alter a patient s metabolism. Reversible inhibition of noncooperative enzymes is classified into three groups which can be distinguished kinetically and which have different mechanisms and effects when administered. The classes are called competitive, uncompetitive, and noncompetitive inhibition. Mixed inhibition also occurs. In all these types of inhibition, the inhibitor (usually a small molecule) binds reversibly and rapidly with the enzyme. 

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... 

Fig. 7.1 Chemical reaction mechanism representing a biochemical NAND gate. At steady state, the concentration of species 85 is low if and only if the concentrations of both species Ii and I2 are high. All species with asterisks are held constant by buffering. Thus, the system is formally open although there are two conservation constraints. The first constraint conserves the total concentration of S3 -F 84 -F 85, and the second conserves -F 87. All enzyme-catalyzed reactions in this model are governed by simple Michaelis-Menten kinetics. Lines ending in over an enzymatic reaction step indicate that the corresponding enzyme is inhibited (noncom-petitively) by the relevant chemical species. We have set the dissociation constants, Kp j, of each of the enzymes Ei-Eg, from their respective substrates equal to 5 concentration units. The inhibition constants, K i and K 2, for the noncompetitive inhibition of E1 and 7 by 11 and I2, respectively, are both equal to 1 unit. The Vmax for both Ej and E2 is set to 5 units, and that for E3 and E4 is 1 unit/s. The Vmax s for E5 and Eg are 10 and 1 units/s, respectively. (From [1].)...

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