Enzymes activity and inhibition

G. A mass spectrometry plate reader monitoring enzyme activity and inhibition with a desorption/ ionization on silicon (DIOS) platform. ChemBioChem 2004, 5, 921-927. 

Unfortunately, however, there is evidence that achieving sufficient fluoride levels in vivo to impair enzyme activity and inhibit bacterial growth is difficult [44], It may therefore be that such potential action of fluoride, for example on car-iogenic bacteria such as S. mutans, has little or no part to play in practical caries prevention. 

Action fats, influencing cellular growth, enzyme activation and inhibition, and... 

Enzyme activity and inhibition of enzyme activity were performed using the method of Chrysler (1). Although test results were not supplied by the author, experimental agents appearing in Table 1 were especially preferred. 

Fluorogenic Substrates, Guilbault and Kramer (20) pubhshed a method using a fluorometric assay for anticholinesterase compoimds. The substrates used were nonfluorescent compounds, the acetyl and butyl esters of 1- and 2-naphthol, which are hydrolyzed by cholinesterase to highly fluorescent materials. The rate of change of fluorescence was related to enzyme activity, and inhibition was measured by decreased rate of change in the production of fluorescence. 

M. Meldal, P. M. St. Hilaire, M. Willert, J. Rademann. M. Grotli, J. Buchardt, C. H. Gotfredsen, M. A. Juliano, L. Juliano "Investigation of enzyme activity and inhibition in the interior of novel solid supports in Proc. 5 th Chinese Pepl. Symp., Chendu 1998. Kluwer Academic Publishers, Dord-recth, 1999, in press. 

M. Meldal Combinatorial solid phase assay for enzyme activity and inhibition in Combinatorial Peptide Libraries. (Ed Shmuel C), Humana Press, Totowa, New Jersey, 1998, pp. 51-82. 

The appHcabihty of DIOS-MS to monitor enzyme activity and inhibition studies has been reported [144, 145]. The viability of this system to monitor enzyme activ-... 

These latter two methods of enzyme activation and inhibition are of profound importance in the control and integration of metabolism and are dealt with in Chapter 23. 

Typically, neurotoxic effects of drugs on monoamine neurons have been assessed from reductions in brain levels of monoamines and their metabolites, decreases in the maximal activity of synthetic enzymes activity, and decreases in the active uptake carrier. In the present study, the traditional markers described above have been used, including the measurement of the content of monoamines and their metabolites in brain at several different timepoints following drug administration. Since reports in the literature have documented that MDMA and MDA can inhibit the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin synthesis (Stone et al. 1986 Stone et al. 1987). it is unclear whether MDMA-induced reductions in the content of serotonin and its metabolite 5-hydroxyin-doleacetic acid (5-HlAA) may be due to suppressed neurotransmission in otherwise structurally intact serotonin neurons or may represent the eonsequenee of the destruction of serotonin neurons and terminals. 

The reported (14) mechanisms of action of allelochemlcals Include effects on root ultrastructure and subsequent Inhibition of Ion absorption and water uptake, effects on hormone-induced growth, alteration of membrane permeability, changes In lipid and organic acid metabolism, inhibition of protein synthesis and alteration of enzyme activity, and effects on stomatal opening and on photosynthesis. Reduced leaf water potential Is one result of treatment with ferulic and p-coumaric acids (15). Colton and Einhellig (16) found that aqueous extracts of velvetleaf (Abutllon theophrastl Medic.) Increased diffusive resistance In soybean fGlycine max. (L.) Merr.] leaves, probably as a result of stomatal closure. In addition, there was evidence of water stress and reduced quantities of chlorophyll In Inhibited plants. 

The initial hydroxylation of tryptophan, rather than the decarboxylation of 5-HTP, appears to be the rate-limiting step in serotonin synthesis. Therefore, the inhibition of this reaction results in a marked depletion of the content of 5-HT in brain. The enzyme inhibitor most widely used in experiments is parachlorophenylalanine (PCPA). In vivo, PCPA irreversibly inhibits tryptophan hydroxylase, presumably by incorporating itself into the enzyme to produce an inactive protein. This results in a long-lasting reduction of 5-HT levels. Recovery of enzyme activity, and 5-HT biosynthesis, requires the synthesis of new enzyme. Marked increases in mRNA for tryptophan hydroxylase are found in the raphe nuclei 1-3 days after administration of PCPA [6]. 

Although substrates may enhance or inhibit their own conversion, as noted in Section 10.4.1, other species may also affect enzyme activity. Inhibitors are compounds that decrease observable enzyme activity, and activators increase activity. The combination of an inhibitor or activator with an enzyme may be irreversible, reversible, or partially... 

Allosteric enzymes have sites other than the catalytic or active site which are associated with the activation and inhibition of the enzyme. 

Allosteric enzymes show various activation and inhibition effects which are competitive in nature and related to conformational changes in the structure of the enzyme. Such allosteric enzymes are often crucial enzymes in metabolic pathways and exert control over the whole sequence of reactions. The name allostery refers to the fact that inhibition of the enzyme is by substances that are not similar in shape to the substrate. 

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