Inhibition and activation

Eberhard, A. (1972). Inhibition and activation of bacterial luciferase synthesis. J. Bacteriol. 109 1101-1105. 

Reactant molecules cause the substrate inhibition and activation discussed in Section 12.1.1. These eflects and deactivation can also be caused by other molecules and by changes in environmental conditions. 

Studies on inhibiting and activating agents of enzymes are important for understanding the mechanisms and alterations in metabolic disorders. 

In Table 2 is given a synopsis of known inhibiting and activating compounds for G-6-PDH and 6-PGDH. 

While iso-enzymes show regular variations in their molecular structure, it is the difference in their catalytic activity that is most significant. They often show different inhibition and activation effects, permitting one iso-enzyme to function under conditions that would reduce the activity of another and it is likely that such variations aid the control of the same reaction under different cellular or tissue conditions. 

Ivanetich KM, Thumser AE, A. 1987. Reversible inhibition and activation of hepatic GSH S-transferases by ethylene dibromide. Pharmac Ther 33 85,88. 

Calpains are enzymes that consist of a proteolytic subunit and a calcium binding subunit. In the cytosol, these enzymes are inactive due to binding of the inhibitory protein, calpastatin. Attachment to the cell membrane removes this inhibition and activation occurs at low concentrations of Csi ions. The enzymes hydrolyse proteins as far as peptides complete hydrolysis requires peptidases, which are also present in the cytosol. 

At the cellular level, plant secondary metabolites have five major effects on herbivores (a) alteration of DNA replication, RNA transcription, and protein synthesis (b) alteration of membrane transport processes (c) enzyme inhibition and activation (d) blocking of receptor sites for endogenous chemical transmitters and (e) affecting the conformation of other macromolecules (Robinson, 1979). 

Szklarz, G. D. and Halpert, J. R. (1998) Molecular basis of P450 inhibition and activation implications for drug development and drug therapy. Drug Metab. Dispos. 26, 1179-1184. 

Solid lines standard titration curves, broken lines manifold systematic variations, arrows direction of the induced relative shift. F s. 1 and 2 simulate structural changes in the ligand-free complexes. Figs 3-6 inhibition and activation processes induced by the controlling ligand (kinetic control). Figs 7 and 8 simulate a variation of the catalytic concentration (see Scheme 3.3-4) or of the constants of association of L to M (thermodynamic control). 

Jinsart, W. Ternai, B. Polya, G.M. Inhibition and activation of wheat embryo calcium-dependent protein kinase and inhibition of avian myosin light chain kinase by long chain aliphatic amphiphiles. Plant Sci., 78, 165-175 (1991)... 

Figure 9-13 (A) An enzyme with binding sites for allosteric inhibitor I and activator J. Conformer A binds inhibitor I strongly but has little affinity for activator J or for substrate S. Conformer B binds S and catalyzes its reaction. It also binds activator J whose presence tends to lock the enzyme in the "on" conformation B. Conformers A and B are designated T and R in the MWC model of Monod, Wyman, and Changeux.80 (B) Inhibited and activated dimeric enzymes.

Tire effects of inhibitors or activators on the kinetics of the monomeric enzyme of Fig. 9-13 can be described by Eq. 9-62 to 9-64. Separate terms for both inhibition and activation can be included. Tire equilibrium between the two conformers can also be indicated explicitly according to Eq. 7-30. However, for monomeric enzymes it is usually not profitable to try to separate the two constants Kt and KttX which describe the conformational change and binding of substrate or activator, respectively, in Eq. 7-30. 

Synthesis of purines is under complex control.273 Some of the mechanisms found in bacteria are outlined in Fig. 25-16. Both feedback inhibition and activation are involved. Very important is the fact that GTP is needed in the synthesis of ATP, and that ATP is needed for synthesis of GTP. This kind of control ensures that an excess of either nucleotide will not be formed for long. In bacteria all of the final end product nucleotides inhibit the initial reaction of step a in Fig. 25-15. 

Figure 25-16 Control of the conversion of inosine 5 -phosphate to the adenine and guanine ribonucleotides and deoxyribonucleotides in bacteria by feedback inhibition and activation.

In all unicellular organisms and in most cells of multicellular organisms, these regulatory enzymes are sensitive to inhibition and activation by small molecules that reflect the metabolic state of the cell. When an effector binds to the regulatory site of an enzyme, it encourages the enzyme to... 

The manner in which the reduction of ribonucleotides to deoxyribonucleotides is regulated has been studied with reductases from relatively few species. The enzymes from E. coli and from Novikoff s rat liver tumor have a complex pattern of inhibition and activation (fig. 23.25). ATP activates the reduction of both CDP and UDP. As dTTP is formed by metabolism of both dCDP and dUDP, it activates GDP reduction, and as dGTP accumulates, it activates ADP reduction. Finally, accumulation of dATP causes inhibition of the reduction of all substrates. This regulation is reinforced by dGTP inhibition of the reduction of GDP, UDP, and CDP and by dTTP inhibition of the reduction of the pyrimidine substrates. Because evidence suggests that ribonucleotide reductase may be the rate-limiting step in deoxyribonucleotide synthesis in at least some animal cells, these allosteric effects may be important in controlling deoxyribonucleotide synthesis. 

In general, it may be said, if /8-glucuronidase undergoes loose combination with other molecules, then variable inhibition and activation must be expected, with or without changes in the shape of the pH-activity curve. 

Qazi and Khachatourians (2007) reported proteases with gelatinase activity released by hydrated conidia of M. anisopliae inhibition and activation studies revealed the presence of various spore-associated metalloprotease isozymes. 

Koley AP, Buters JTM, Robinson RC, et al. Differential mechanisms of cyto-chrome-P450 inhibition and activation by alpha-naphthoflavone. J Biol Chem 1997 272 3149-3152. 

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