Enzymatic action activity

The thrombin receptor is unusual in that the receptor is activated by the enzymatic action of thrombin which cleaves the N-terminus of the receptor leaving the receptor constitutively active. 

Chemistry. Nicotinamide (NAm), a product of PARP-1 enzymatic action on NAD and a weak inhibitor of PARP-1 activity (Curtin, 2006), was used as a model for the first PARP-1 inhibitors, including benzamide and 3-aminobenzamide (3AB) (Shall, 1975) (Fig. 7a). Benzamide and 3AB inhibit PARP-1 activity in the mM range and may also inhibit other PARP family members e.g., PARP-2 and tankyrase Smith et al, 1998 Ame et al, 1999), thus lacking the potency and specificity required for therapeutic purposes. Banasik et al developed 1,5-dihydroisoquinoline (Fig. 7c) and a variety of other inhibitors (Banasik et al, 1992), which were used in turn to develop even more inhibitors with greater specificity. 

Mode of action Activation of macrophages/monocytes release of endogenous mediators such as lipids from arachidonic acid, reduced oxygen species, proteins 1. Pore formation in cell membranes 2. Enzymatic modification of specific substrates in the cytosol of host cells (AB-type toxins) 3. Superantigen stimulation of the immune system... 

Bertrand, in 1897, observed that certain enzymes required dialysable substances to exert catalytic activity. He named these substances coenzymes . Sorensen pointed out the dependence of enzyme activity on pH in 1909 (Sumner and Somers, 1953). An important step entering physico-chemistry, and hence extending the theoretical basis of enzymology, were the kinetic investigations and their interpretation by Michaelis and Menten. They postulated that enzymatic action is due to the formation of an intermediate compound between enzyme and substrate, and they presented a mathematical form still used today (Sumner and Myrback, 1950). 

The active site of COMT consists of the AdoMet binding domain and the catalytic site. The structural elements and individual interactions between COMT residues and the enzymatic-action-participating ligands are demonstrated in detail in Figures 5 to 8. 

Impressed by the specificity of enzymatic action, biochemists early adopted a "lock-and-key" theory which stated that for a reaction to occur the substrate must fit into an active site precisely. Modem experiments have amply verified the idea. A vast amount of kinetic data on families of substrates and related competitive inhibitors support the idea and numerous X-ray structures of enzymes with bound inhibitors or with very slow substrates have given visual evidence of the reality of the lock-and-key concept. Directed mutation of genes of many enzymes of known three-dimensional structure has provided additional proof. 

Since microbial activity and growth are manifestations of enzymatic action, and since the rates of enzyme reactions increase... 

The development in this area of enzymatic action on the various damaged DNA sites continues to be very active. For this reason, only a very short account has been given as a kind of flavor for the reader to see in which direction research in this field seems to expand. 

Formate. .. is quite unreactive under physiological conditions and must be activated to serve as an efficient formylating agent. The fundamental importance of [THF] is to maintain formaldehyde and formate in chemically poised states, not so reactive as to pose toxic threats to the cell but available for essential processes by specific enzymatic action. 

Figure 16.2 Dihydropyridine-pyridinium salt redox system for site-specific and sustained delivery to the brain. The prodrug A is delivered directly to the brain, where it is oxidized and trapped as the prodrug B. The quaternary ammonium salt is slowly cleaved by chemical/enzymatic action with sustained release of the biologically active phenylethylamine C and the facile elimination of the carrier molecule D. Elimination of the drug from the general circulation is by comparison accelerated, either as A or B or as cleavage products...

Despite the broad range of possible actions of GPCRs, they all share a common seven a-helical transmembrane motif of the structure. The ligand binding site is located either at the extracellular region or within the transmembrane a-helical bundle, and the cytoplasmic loops are responsible for coupling to G proteins and activate them (GPCRs act in an enzymatic way) whereas other proteins like arrestins stop enzymatic action of these receptors. 

As for any new lot of material, assessments of biological activity should be performed to demonstrate the efficacy of the product. This may be achieved though the use of animal-based biological assays, cell-based assays that evaluate the material at the cellular level, and biochemical activity assays such as enzymatic action. Standards should be properly defined. Potency and efficacy for individual lots of material can therefore be defined. 

As pointed out by Westlake and San Antonio (46) such factors as temperature, light, humidity, air movement, volatility of the compounds, and microorganism activity are influencing the breakdown and mechanical dispersion of residues on plant surfaces and in soils. However, within plants and animals, probably the most important single factor in pesticide breakdown and transformation is through enzymatic action. As shown in Figure 1, when a pesticide is applied to plants, animals, soils, water or air, there are many factors that may effect chemical changes, and the rates of such alterations will depend on the nature of the compound and the particular environmental conditions to which... 

---