Enzyme, adaptation

Fig. 11.4. Model for cholinergic signalling in the intestinal mucosa, providing a possible rationale for AChE secretion by parasitic nematodes. ACh released from enteric cholinergic motor neurons stimulates chloride secretion, mucus secretion and Paneth cell exocytosis through muscarinic receptors. Secretory responses may be modulated by mast cell mediators, either directly or via the induction of neural reflex programmes. The role of muscarinic receptor-positive cells in the lamina propria of rats infected with N. brasiliensis is undetermined, as are potential mechanisms of trans-epithelial transport of the enzymes. Adapted from Cooke (1984).

Tab. 3.2 Characteristics of studied enzymes (Adapted from Refs. [55,56]).

Fig. 22. A model for the interaction of Li(I) with the enzyme inositol monophosphatase. Lithium(I) occupies the second Mg(II) site in the enzyme. Adapted from (479). 

Table 3.2 Some important therapeutic enzymes (adapted from Chaplin and Bucke, 1990).

Table 13.2 A comparison of the costs of some common commercial enzymes (Adapted from Poldermans, 1989).

Figure 9.2. The inherent metabolic flexibility of the isoprenoid pathway leading to the synthesis of some carotenoid pigments. Genes coding for two enzymes capable of acting on carotenoid structures were introduced into Escherichia coli which had already been transformed to give it the capacity to make p,p-carotene. Both of the two introduced new enzymes (one shown with red arrows and the other with blue arrows) acted on multiple substrates because of their lack of specificity. The resulting matrix of transformations means that nine different products can be made by just two tailoring enzymes. (Adapted from Umeno et al. ° who used data from Misawa et al. °)...

FIGURE 4. Active sites of some dinuclear zinc enzymes. Adapted with permission from Reference 9. Copyright (2004) ACS... 

Ziegler DM (1990) Flavin-containing monooxygenases enzymes adapted for multisubstrate specificity. Trends Pharmacol Sci 11 321-324... 

A particular type of biosensor can be developed by putting a membrane in contact with the semi-conducting layer of a field effect transistor. If the membrane incorporates an enzyme adapted to transform a particular analyte (Fig. 19.8), reaction of that enzyme will modify the polarity at the surface of the insulating layer. This will in turn modify the conduction between the source and the collector of the field effect transistor. The current flowing through these two electrodes (source and collector) serves as the signal. 

Figure 3 Bar graph showing uptake of glncocengbrosldase by hcpaiocytcs and non-panoichymfll cells isolated from rat liver alter inflnion of 5.7 U of native or 5.0 U of mannose-terminal enzyme. (Adapted from Ref. 22.)...

The argument previously outlined provides an appealing physiochemi-cal explanation for the stability and activity behavior of homologous enzymes adapted to different temperatures. However, one cannot interpret the behavior of a biological system solely in physiochemical terms. All these enzymes are the products of evolution. While they are certainly subject to the laws of physics and chemistry, the evolutionary process imposes its own, additional constraints. We will see that the stability-activity trade-off is not a necessary characteristic of enzymes, especially not those evolved in the laboratory. 

Fig. 3. Homologous enzymes adapted to different temperatures show a trade-off between catalytic activity at low temperatures (high for enzymes from psychrophilic organisms, but generally low for enzymes from thermophiles) and thermostability (high for thermophilic enzymes, but low for enzymes from psychrophiles). These natural enzymes lie in the darker shaded area, which is bounded on one side by the minimal stability and activity required for biological function. Enzymes that are both highly thermostable and highly active at low temperature (lighter shaded area) are generally not found in nature.

Supercriticality in an environment does not, in itself, prohibit life. Some terran enzymes are known to be active in supercritical fluids.30-32 Subsequent reviews can be found in Aaltonen and Rantakyla,33 Kamat et al.,34 and Aaltonen.35 Although most of that work concerns supercritical carbon dioxide as the solvent, fluorinated hydrocarbons (HCF3) and simple alkanes (e.g., ethane, propane) have also been reported,36 providing a formal demonstration that terran-derived proteins can function in these media. Any enzyme adapted to the supercritical media would undoubtedly be different from those used in the studies cited. 

There are over 2,500 different biochemical reactions with specific enzymes adapted for their rate enhancement. Since different species of organism produce different structural variants of enzymes, the number of different enzyme proteins in all of biology is well in excess of 106. Each enzyme is characterized by specificity for a narrow range of chemically similar substrates (reactants) and also other molecules that modulate their activities these are called effectors and can be activators, inhibitors, or both in more complex enzymes, one compound may have either effect, depending on... 

Fig. 9.4. Schematic illustration of modular protein evolution, exemplified on proteases, involved in blood coagulation and fibrinolysis. Varying type and number of modules, fused onto a common protease unit, generates a family of highly specific hydrolytic enzymes. (Adapted from [56])...

Fig. 4 Structure of the building blocks for a DCL designed to generate possible UDP-galactose mimics. Amplification of the constitutional dynamic library (CDL) against catalytically active al,3GalT and pi,4GalT enzymes (adapted from [45])...

Holloszy, J. 0., Oscal, L. B., Don, I. J. and Mole, P.A. (1970) Mitochondrial citric acid cycle and related enzymes adaptive response to exercise. Blochem. Blophys. Res. Commun. 40 1368-73. 

Figure 11.2 Kinetic plots (initial rate versus sucrose concentration) of fructosyltransferase from A aculeatus. Transfer activity ( ) and hydrolytic activity (o). Reactions were carried out in 0.2 M sodium acetate buffer (pH 5.5) at 60°C. Kinetic parameters were calculated estimating a molecular mass of 135 kDa for the active enzyme. Adapted from Ref [33].

Enterohepatic circulation of bile acids 36 12.4.2 Enzyme adaptation 54... 

In the course of evolution and during the short life-span of every human being, it was - and still is - necessary for the performance of enzyme systems involved in biotransformation to adapt permanently to the requirements of life. This enzyme adaptation is achieved by four mechanisms ... 

FIGURE 12.9 Reactions catalysed by SDR enzymes. (Adapted from Kavanagh, drnvall, Persson, i4 Oppermann, 2008.)... 

FIGURE 12.17 Metal coordination sites in trinuclear zinc enzymes. (Adapted from Parkin, 2004.)... 

Molecular Mechanisms of Enzyme Adaptation How Enzymes Regulate Metabolism 150... 

The present chapter focuses on the effects of environmental stress on enzyme structure and function and the various mechanisms that respond to these stresses to alter enzyme function (and metabolic pathways). Many examples will be drawn from animals that live at environmental extremes, for it is here that we find the principles of enzyme structure and function most clearly illustrated. Because this subject is complex and covers a wide variety of different fields, the present chapter will highlight key principles using selected enzymes as examples. The reader is referred to other sources for more exhaustive treatments of individual topics in comparative biochemistry and enzyme adaptation (Crowe and Clegg, 1978 Ho-chachka and Somero, 1984 Gilles, 1985 Bowler and Fuller, 1987 Storey, 1988 Storey and Storey, 1988). 

MOLECULAR MECHANISMS OF ENZYME ADAPTATION HOW ENZYMES REGULATE METABOLISM... 

All enzymes are catalysts which act to increase reaction rates. In fact, in most cases, the difference between enzyme catalyzed and noncatalyzed reactions is so great that only the enzyme-catalyzed reactions occur to any significant extent in vivo. Exactly how enzymes participate in this process has been detailed earlier in this book and will not be reviewed here. However, in order to understand enzyme adaptation, it is essential that a few basics of enzyme kinetics be reviewed. The basic enzyme mechanism describes the case where a single substrate binds to an enzyme before being chemically converted to a product. Although the majority of enzyme-catalyzed reactions are two-substrate reactions, several can be adequately described by this mechanism and an understanding of this mechanism is essential... 

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