Enzymes Fundamentals

E. Khalikova, P. Susi, and T. Korpela, Microbial dextran-hydrolyzing enzymes Fundamentals and apphcations, Microbiol Mol Biol Rev., 69 (2), 306-325, 2005. 

Unidirectional (membrane type) steady-state equations of diffusion-reactions with one Michaelis type enzyme. Fundamental case no regulatory effects zero order reaction, v = Vm, assumption 10 Km or s 10 to 50 in all points of the membrane. 

D-Mevalonic acid is the fundamental intermediate in the biosynthesis of the terpenoids and steroids, together classed as poly-isoprenoids. The biogenetic isoprene unit is isopentenyl pyrophosphate which arises by enzymic decarboxylation-dehydration of mevalonic acid pyrophosphate. D-Mevalonic acid is almost quantitatively incorporated into cholesterol synthesized by rat liver homogenates. 

The process of target identification analyzes a complex disease process by dissecting it into its fundamental components. This makes it possible to identify the one that is most integral to the manifestation of the disease. Target identification aims to understand the biological processes related to a disease, and to identify its mechanism and the structure of individual elements of the disease. Commonly these individual elements are receptors, enzymes, etc., which become the target of new drugs. 

We 11 see numerous examples of both reaction types m the following sections Keep m mind that m vivo reactions (reactions m living systems) are enzyme catalyzed and occur at far greater rates than those for the same transformations carried out m vitro ( m glass ) m the absence of enzymes In spite of the rapidity with which enzyme catalyzed reactions take place the nature of these transformations is essentially the same as the fundamental processes of organic chemistry described throughout this text... 

Many globular proteins are enzymes They accelerate the rates of chemical reactions m biological systems but the kinds of reactions that take place are the fundamental reactions of organic chemistry One way m which enzymes accelerate these reactions is by bringing reactive func tions together m the presence of catalytically active functions of the protein... 

Mode of Action. The fundamental biochemical lesion produced by arsenicals is the result of reaction between As " and the sulfhydryl groups of key respiratory enzymes such as pymvate and a-ketoglutarate dehydrogenases. 

Once kiside the host ceU, the vims must repHcate its own nucleic acid. To do this, it often uses part of the normal synthesizing machinery of the host ceU. If the vims is to continue its growth cycle, vkal nucleic acid and vkal proteki must be properly transported within the ceU, assembled kito the kifective vims particle, and ultimately released from the ceU. AH of these fundamental processes kivolve an intimate utilization of both ceUular and vkal enzymes. Certain enzymes that ate kivolved ki this process ate specificaHy suppHed by the invading vims. It is this type of specificity that can provide the best basis for antivkal chemotherapy Thus an effective antivkal agent should specificaHy inhibit the vkal-encoded or vims-kiduced enzymes without inhibition of the normal enzymes involved in the biochemical process of the host ceH. Vims-associated enzymes have been reviewed (2,3) (Table 1). 

Chemical Aspects of Enzyme Technology—Fundamentals, Plenum Press, New York, 1990. Various eds.. Enzyme Engineeiing, vols. 2-5, Plenum Press, New York, 1974—1980. Wingard, L. B., I. V. Berezin, and A. A. Klyosov (eds.). Enzyme Engineeiing—Future Directions, Plenum Press, 1980. 

In this chapter we shall illustrate some fundamental aspects of enzyme catalysis using as an example the serine proteinases, a group of enzymes that hydrolyze peptide bonds in proteins. We also examine how the transition state is stabilized in this particular case. 

Biocatalyst An enzyme tliat plays a fundamental role in living organisms or in industry by activating or accelerating a bioprocess. 

The biological transfonnations that involve ATP are both numerous and fundamental. They include, for example, many phosphorylation reactions in which ATP transfers one of its phosphate units to the —OH of another molecule. These phosphorylations are catalyzed by enzymes called kinases. An example is the first step in the metabolism of glucose ... 

Like the examples above, dihydroxyacetanilide epoxidase (DHAE) uses an olefin as the substrate for epoxidation. Its mechanism, however, is fundamentally different from those of cytochrome P450 or flavin-dependent enzymes. Dihydroxyacetanilide is an intermediate in the biosynthesis of the epoxyquinones LL-C10037a, an antitumor agent produced by the actinomycete Streptomyces LL-C10037 [75, 76], and MM14201, an antibiotic produced by Streptomyces MPP 3051 (Scheme 10.20) [77]. The main structural difference between the two antibiotics lies in the opposite stereochemistry of the oxirane ring. 

Hurst (19) discusses the similarity in action of the pyrethrins and of DDT as indicated by a dispersant action on the lipids of insect cuticle and internal tissue. He has developed an elaborate theory of contact insecticidal action but provides no experimental data. Hurst believes that the susceptibility to insecticides depends partially on the cuticular permeability, but more fundamentally on the effects on internal tissue receptors which control oxidative metabolism or oxidative enzyme systems. The access of pyrethrins to insects, for example, is facilitated by adsorption and storage in the lipophilic layers of the epicuticle. The epicuticle is to be regarded as a lipoprotein mosaic consisting of alternating patches of lipid and protein receptors which are sites of oxidase activity. Such a condition exists in both the hydrophilic type of cuticle found in larvae of Calliphora and Phormia and in the waxy cuticle of Tenebrio larvae. Hurst explains pyrethrinization as a preliminary narcosis or knockdown phase in which oxidase action is blocked by adsorption of the insecticide on the lipoprotein tissue components, followed by death when further dispersant action of the insecticide results in an irreversible increase in the phenoloxidase activity as a result of the displacement of protective lipids. This increase in phenoloxidase activity is accompanied by the accumulation of toxic quinoid metabolites in the blood and tissues—for example, O-quinones which would block substrate access to normal enzyme systems. The varying degrees of susceptibility shown by different insect species to an insecticide may be explainable not only in terms of differences in cuticle make-up but also as internal factors associated with the stability of oxidase systems. 

An examination of the autocorrelation function (0(0) <2(0) annucleophilic attack step in the catalytic reaction of subtilisin is presented in Fig. 9.4. As seen from the figure, the relaxation times for the enzymatic reaction and the corresponding reference reaction in solution are not different in a fundamental way and the preexponential factor t 1 is between 1012 and 1013 sec-1 in both cases. As long as this is the case, it is hard to see how enzymes can use dynamical effects as a major catalytic factor. 

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