Enzyme theory, adaptive

Adaptive Enzyme Theory. The aliesterases are largely found in the microsomes of rat liver cells (44). Recently Hart and Fouts (51,52, 67-69) have presented evidence that in vivo administration of chlordan or chemically related DDT stimulates the activity of hepatic microsomal drug-metabolizing enzymes, as evidenced by proliferation of smooth-surfaced endoplasmic reticulum (SER) which was first noted with phenobarbital. Several reviews of hepatic drug metabolism... 

The first chapter by Moszyliski presents in a systematic and comprehensive manner the current state-of-the-art theory of intermolecular interactions. Numerous examples illustrate how theoreticians and experimentalists working in tandem may gather valuable quantitative results related to intermolecular interactions, like accurate potential functions, interaction-induced properties, spectra and collisional characteristics or dielectric, refractive or thermodynamic properties of bulk phases. On the other hand the most advanced Symmetry Adapted Perturbation Theory (SAPT) enables validation of more approximate variation-pertubation models which could be applied to the analysis of specific interactions in much larger molecular systems, for example enzyme-drug interactions discussed in Chapter VIII by Berlicki et al. 

Several copper enzymes will be discussed in detail in subsequent sections of this chapter. Information about major classes of copper enzymes, most of which will not be discussed, is collected in Table 5.1 as adapted from Chapter 14 of reference 49. Table 1 of reference 4 describes additional copper proteins such as the blue copper electron transfer proteins stellacyanin, amicyanin, auracyanin, rusticyanin, and so on. Nitrite reductase contains both normal and blue copper enzymes and facilitates the important biological reaction NO) — NO. Solomon s Chemical Reviews article4 contains extensive information on ligand field theory in relation to ground-state electronic properties of copper complexes and the application of... 

The use of the symbol E in 5.1 for the environment had a double objective. It stands there for general environments, and it also stands for the enzyme considered as a very specific environment to the chemical interconversion step [102, 172], In the theory discussed above catalysis is produced if the energy levels of the quantum precursor and successor states are shifted below the energy value corresponding to the same species in a reference surrounding medium. Both the catalytic environment E and the substrates S are molded into complementary surface states to form the complex between the active precursor complex Si and the enzyme structure adapted to it E-Si. In enzyme catalyzed reactions the special productive binding has been confussed with the possible mechanisms to attain it lock-key represents a static view while the induced fit concept... 

Complexation could occur in many different ways, but for the intimate com-plexation required for catalysis, the enzyme must have, or must be able to assume, a shape complementary to that of the substrate. Originally, it was believed that the substrate fitted the enzyme somewhat like a key in a lock this concept has been modified in recent years to the induced-fit theory, whereby the enzyme can adapt to fit the substrate by undergoing conformational changes (Figure 25-18), Alternatively, the substrate may be similarly induced to fit the enzyme. The complementarity is three-dimensional, an important factor in determining the specificity of enzymes to the structure and stereochemical configuration of the substrates. 

The hexokinase molecule changes shape drastically on binding to substrate, consistent with the induced-fit theory of an enzyme adapting itself to its substrate. 

A limitation of the lock-and-key theory is the implication that enzyme conformations are fixed or rigid. However, research results suggest that the active sites of some enzymes are not rigid. This is taken into account in a modification of the lock-and-key theory known as the induced-fit theory, which proposes that enzymes have somewhat flexible conformations that may adapt to incoming substrates. The active site has a shape that becomes com-planentary to that of the substrate only after the substrate is bound (see I Figure 10.4B). 

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