Noncompetitive inhibition, competitive

Michaelis-Menten kinetics Myoglobin binding to oxygen Cooperative binding Competitive inhibition Noncompetitive inhibition... 

Unlike competitive inhibition, noncompetitive inhibition cannot be reversed by the addition of more substrate because additional substrate has no effect on the enzyme-bound inhibitor (it can t displace the inhibitor because it can t bond to the site occupied by the inhibitor). 

Effect of the concentration of inhibitor on the Lineweaver-Burk plots for (a) competitive inhibition, (b) noncompetitive inhibition, and (c) uncompetitive inhibition. The inhibitor s concentration increases in the direction shown by the arrows. 

Adenylyl Cyclases. Figure 6 Adenylyl cyclase catalytic cycle. Points during the catalytic cycle of adenylyl cyclases at which inhibition by competitive and noncompetitive nucleotides occur E represents the catalytic transition state. 

Inhibition. Consider the case of competitive inhibition. Show a family of Lineweaver-Burk lines as [I] increases, including the line for [I] = 0. Construct the plots carefully so as to show how the x- and y-intercepts vary. Do the same for noncompetitive inhibition. 

KINETIC ANALYSIS DISTINGUISHES COMPETITIVE FROM NONCOMPETITIVE INHIBITION... 

Double reciprocal plots distinguish between competitive and noncompetitive inhibitors and simpbfy evaluation of inhibition constants Aj. v, is determined at several substrate concentrations both in the presence and in the absence of inhibitor. For classic competitive inhibition, the lines that connect the experimental data points meet at they axis (Figure 8-9). Since they intercept is equal to IIV, this pattern indicates that wben 1/[S] approaches 0, Vj is independent of the presence of inhibitor. Note, however, that the intercept on the X axis does vary with inhibitor concentration—and that since is smaller than HK, (the apparent... 

To refer to the kinetics of allosteric inhibition as competitive or noncompetitive with substrate carries misleading mechanistic implications. We refer instead to two classes of regulated enzymes K-series and V-se-ries enzymes. For K-series allosteric enzymes, the substrate saturation kinetics are competitive in the sense that is raised without an effect on V. For V-series allosteric enzymes, the allosteric inhibitor lowers... 

Two additional characteristics of the inhibition of mineral absorption by phenolic acids were observed. The inhibition of both P0 absorption (27) and K+ absorption (31, 32) was reversed when the phenolic acid was removed from the absorption solution. Harper Balke (32) found this reversibility to be dependent upon pH the lower the pH, the less the reversal. Also, kinetic plots of the inhibition of mineral absorption showed that the phenolic acids did not competitively inhibit either P0 (26, 28) or K+ (31) absorption. Rather, ferulic acid inhibited PO -absorption in a noncompetitive (26) or uncompetitive (28) manner and jr-hydroxybenzoic acid inhibited K+ absorption in an uncompetitive manner (31). 

Figure 3.2 Cartoon representations of the three major forms of reversible inhibitor interactions with enzymes (A) competitive inhibition (B) noncompetitive inhibition (C) uncompetitive inhibition. Source-. From Copeland (2000).

These three classes of inhibition can be distinguished by virtue of the effect of variations in inhibitor concentration on the slopes and intercepts of reciprocal plots. For competitive inhibition only the slope varies. For uncompetitive inhibition only the intercept varies, while for noncompetitive inhibition both the slope and the intercept vary. 

The type of interaction of verapamil (solid bar) in the presence of one of the other compounds is indicated Cooperative stimulation (hatched bars) allosteric noncompetitive inhibition (cross-hatched bars) and competitive inhibition (gray bars). (Adapted from Ref. [57].)... 

The presence of some substances may hinder the action of an enzyme. Such substances are known as inhibitors, and in some cases the inhibitor may be a metal. It is not necessary to describe all the ways in which an inhibitor may reduce the activity of an enzyme, but one way is by binding to the substrate. This is known as competitive inhibition, and it applies to cases in which the inhibitor competes with the substrate in binding to the enzyme. In noncompetitive inhibition, the inhibitor binds to the enzyme and alters its structure so it can no longer bind to the substrate. In some instances, certain metal ions function as inhibitors of enzyme action, which can be a cause of the toxicity referred to earlier. 

There are three types of reversible inhibition competitive, uncompetitive, and noncompetitive. Most texts acknowledge only two kinds of inhibition—competitive and noncompetitive (or mixed). This approach makes it difficult to explain inhibition on an intuitive level, so we ll use all three types of inhibition and explain what the other nomenclature means in the last paragraph of this section. 

Figure 2.13 Lineweaver-Burk plot for no inhibitor, competitive, and noncompetitive inhibition.

In steps (1) and (2), S and I compete for (sites on) E to form the binary complexes ES and ET. In steps (3) and (4), the ternary complex EIS is formed from the binary complexes. In steps (5) and (6), ES and EIS form the product P if EIS is inactive, step (6) is ignored. Various special cases of competitive, noncompetitive, and mixed (competitive and noncompetitive) inhibition may be deduced from this general scheme, according to the steps allowed, and corresponding rate laws obtained. 

If we do not make the assumption leading to K2 = K3, then the four-step mechanism above also represents mixed (competitive and noncompetitive) inhibition, and both Km and Vmax change. In this case, equation 10.4-12 may be written as... 

A reciprocal plot of the effect of varying concentrations of a noncompetitive inhibitor on enzyme-catalyzed substrate turnover readily reveals the nature and characteristics of this type of inhibition (Fig. 3.6). Notice that in this case, the properties that characterize noncompetitive inhibition are virtually opposite of those that characterize competitive inhibition. With a noncompetitive inhibitor Emax does change but KM is constant. 

For all intent and purpose, inhibition of CYP enzymes can be classified into two categories reversible (e.g. competitive and noncompetitive) inhibition and mechanism-based (e.g. quasi-irreversible and irreversible) inhibition [93]. The remainder of this chapter will be divided to reflect these two categories of inhibition and will focus solely on CYP-based drug interactions. 

Figure 9.6 Dixon plot representations of competitive (a), noncompetitive (b), uncompetitive (c) and mixed (d) inhibition.

Opioids also interact with excitatory amino acid neurotransmitters. At lower micromolar concentrations, p agonists (e.g., DAMGO) enhance NMDA activity in the nucleus accumbens, but inhibit non-NMDA activity (Martin et al. 1997). At higher concentrations (5 pM), NMDA currents are reduced. Conversely, central administration of glutamate can precipitate a withdrawal syndrome in morphine-dependent animals, similar to the opioid antagonist naloxone. NMDA mechanisms also appear to be involved in the development of morphine tolerance. Competitive and noncompetitive NMDA antagonists and inhibitors of nitric oxide synthase reduce or eliminate tolerance to morphine (Elliott et al. 1995 Bilsky et al. 1996). However, this does not occur for tolerance to k opioids. Pharmacokinetics... 

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