Action and Specificity

Strictly speaking, an enzyme can only provisionally be classified as a /8-glucuronidase before its action has been shown to be purely hydrolytic— by the isolation of D-glucuronic acid as well as the aglycon. This consideration is of particular importance when whole, bacterial suspensions are employed as a source of the enzyme. 

Section IX, 1). Although they have not been systematically studied, nonmammalian /3-glucuronidase preparations appear to resemble the mammalian enzyme in these respects. 

The actions of 3-0-methyl-D-glucuronate and 3-0-methyl-D-glucaro-l, 4-lactone as inhibitors are of interest in this connection (see Table VIII). 

Two further points of interest with regard to the specificity of /3-glu-curonidase are raised by recent reports that leech hyaluronidase is a poly-/ -glucuronidase,211 and that hydrolysis of certain mucopolysaccharides yielded some L-iduronic acid212 oligosaccharides containing this uronic acid resisted hydrolysis by /3-glucuronidase.209 

Adult cats have been found, in experiments with tissue slices and cell- 

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Fig. 2). The staphylococcal enzyme may appear to be more akin in its mode of action to the spleen enzyme because they both hydrolyze DNA and RNA to 3 -nucleotides, whereas the venom enzyme releases 5 -nucleotides. However, their mode of action and specificity are quite different, and the structural requirements of the staphylococcal enzyme substrates are perhaps more nearly similar to those of the venom enzyme. The principal difference is that the staphylococcal enzyme cleaves the diester bond between the phosphate and the 5 -carbon of the sugar, whereas the venom enzyme cleaves on the other side of the phosphate, that is, between the phosphate and the nonspecific hydroxylic component of the diester bond. In contrast to both spleen and venom diesterases, the primary product released by staphylococcal nuclease hydrolysis is a derivative bearing a hydroxyl group (on the 5 position) rather than a phosphoryl group. Therefore, the 3 -phosphoryl product formed from polynucleotide hydrolysis is a secondary consequence of such cleavage. 

Contemporary ideas of drug action and specificity are based on the assumption that the initial process in drug action is the formation of a reversible complex between the drug and a cell component generally known as the drug receptor (Figure 2.2). The interaction of a drug with a specific receptor site is characterized by at least three factors, namely ... 

The minor revolution in our knowledge about molecular aspects of steroid hormone action that has occurred in recent years has led to the questioning of some long-held dogmas, the confirmation of others and the introduction of several new concepts. These are discussed for individual classes of steroid hormone in separate chapters of this volume. This chapter will take a more general Look at molecular aspects of hormone action with an emphasis on two topics the generality of models of action and specificity of action. 

Since the predicted with PASS biological activity spectra contain the estimates of probabilities for the pharmacological main and side effects, molecular mechanisms of action and specific toxicity, the choice of the most prospective compounds from the available samples of chemical compounds can be realized on the basis of complex criteria. Both the presence of targeted biological effects... 

The precise mechanism and sight of action of most compounds categorized as calcium inhibitory compounds, therefore, remains obscure. Future refinements in experimental models and techniques will undoubtedly will lead to the classification of calcium inhibitory compounds based upon their primary mechanism of action and specific site(s) of action (extracellular vs. intracellar). Because of the uncertainty surrounding the precise mechanisms of action of calcium inhibitory compounds, I will describe their cardiac electrical and mechanical effects illuding when possible to those compounds that are believed to act l) competitively with Ca + for specific calcium channels (e.g., Co +, Mn +, La2+, etc.) 2) at the cardiac cell membrane and possibly by one of several intracellular mechanisms (e.g., verapamil, diltiazem, nifedipine) and 3) intracellularly (e.g., 2-n-propyl and 2-n-butyl MDI). 

At this point the plan swings into action, and specific individual programmes start up to implement it. 

The microscopic understanding of how enzymes work, the molecular dynamics of their action and specificity, will certainly remain a challenge for many years. The literature is in fact already full of suppositions, not all of which can be true, because they are often mutually contradictory. One wonders whether progress in understanding the many atom nature of solution reactions will also help us in understanding the many atom nature of enzyme-controlled reactions. 

Little is known about the characteristics or properties of TIP other than the observation that it has a short half-life. Several potential mechanisms have been tested with no success. Compounds which do not inhibit the decay process are (1) energy poisons such as dinitrophenol, 2-deoxy-D-glucose, or rotenone, (2) lysosomal directed agents such as methyl-amine and chloroquine, (3) cholchicine, an inhibitor of microtubule function, and (4) leupeptin, an inhibitor of certain intracellular proteases. Obviously, further experimentation will be necessary to confirm the existence of TIP and to elucidate its identity, mechanism of action, and specificity. 

Knowledge accrued regarding the intestinal microflora, nutrition, immunity, mechanisms of action and specific diseases should be carefully combined with genomic data to allow the development of a second generation of probiotics strains for both site-and disease-specific action. 

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