Enzymatic influences

The toxicity of dimethoate to mice may be increased by pre-treatment with phenobarbitone [58] or pentobarbitone [59], whereas the toxicities of phos-phamidon, dicrotophos and their Ai-dealkylated derivatives are decreased [58]. Dimethoate requires oxidative activation, yet the vinyl phosphates do not. In vitro studies confirm the induction of mouse hepatic microsomal enzymes by phenobarbitone pre-treatment, which activate schradan, mala-thion and parathion [60]. Microsomal induction by pre-treatment with pentobarbitone stimulates not only the activation of certain organophos-phates, but also their catabolism, thereby reducing their toxicity, for example mipafox [59]. 

---

Surprisingly, the 7t-system geometry in a substrate has a notable influence in the enzymatic aminolysis of esters. The reaction of diethyl fumarate with different amines or ammonia in the presence of CALB led to the corresponding trans-amidoesters with good isolated yields, but in the absence of enzyme, a high percentage of the corresponding Michael adduct is obtained (Scheme 7.9). Enzymatic aminolysis of diethyl maleate led to the recovery of the same a, P-unsaturated amidoester, diethyl fumarate, and diethyl maleate. The explanation of these results can be rationalized via a previous Michael/retro-Michael type isomerization of diethyl maleate to fumarate, before the enzymatic reaction takes place. In conclusion, diethylmaleate is not an adequate substrate for this enzymatic aminolysis reaction [23]. 

Murphy SD, DuBois KP. 1958. The influence of various factors on the enzymatic conversion of organic thiophosphates to anticholinesterase agents. J Pharmacol Exp 124 194-202. 

Scheme 5.6 Influence of a cosolvent on enzymatic kinetic resolution.

It has been observed that whereas the catalytic activity of malic dehydrogenase in water is not influenced by pressure, in reversed micelles it shows a bell-shaped dependence, suggesting regulation of the enzymatic activity by pressure application, which cannot be realized in aqueous solutions [180],... 

The value of critical concentration depends strongly on the pectin being used. Figure 2 gives the viscosity curves of two different pectins at the same concentration of 2.5 % w/w. The different production parameters, that have been used for these pectins, have strongly influenced their flow behaviour. The enzymatic reduction of the molecular weight down to... 

There have been many papers reporting studies on the influence of structure and conditions of the medium. Specifically, the kinetic behavior of enzymatic reactions in two-phase media was probed [7,25,27,63]. The reaction localization and the interaction between mass transfer and metabolism in compartmentalized media are interesting phenomena. Their study in the laboratory are useful for optimizing the operating conditions of bioreactors in a preparative scale. In addition, they also help to understand better the behavior of enzymatic systems in vivo. 

For instance, we study here the influence of the surrounding media on the behavior of two enzymatic reactions in two-phase systems ... 

Furthermore, in the system with coupled lipase and lipoxygenase, the production rate of HP is governed by the first enzymatic reaction and mass transfer. When TL,- is small (0 to 1 mM equiv. 3 mM LA), the kinetic curve has a sigmoid shape due to surface active properties of LA and HP [25]. Hydrolysis of TL and the increase of LA favor the transfer of LA. Such a transfer allows the lipoxygenase reaction to progress. Since lipox-ygenation consumes LA and produces HP, catalysis and transfer demonstrates a reciprocal influence. 

Various factors that influence the release of drugs from particulate carriers are listed in Table 10. Drugs can be released by diffusion or by surface erosion, disintegration, hydration, or breakdown (by a chemical or an enzymatic reaction) of the particles. The release of drugs from microspheres follows a biphasic pattern that is, an initial fast release followed by a slower... 

Currently, there are several assays for the measurement of PSA. All of them contain monoclonal or polyclonal antibodies labeled with enzymatic, fluorometric, or radioactive markers. These assays have shown significant variations within the same patient specimens. These variations may result from differences in antibody specificity, reaction kinetics, calibration, or the system s sensitivity. Studies have shown that only free PSA and PSA-ACT show immunological reactivity in these assays. Also, reaction kinetics can influence the molar ratio. Some of these assays with shorter incubation times may specifically bind the free PSA molecule (which is a lower weight form of PSA). In the equimolar assays, changing the incubation... 

Enzymatic reactions are influenced by a variety of solution conditions that must be well controlled in HTS assays. Buffer components, pH, ionic strength, solvent polarity, viscosity, and temperature can all influence the initial velocity and the interactions of enzymes with substrate and inhibitor molecules. Space does not permit a comprehensive discussion of these factors, but a more detailed presentation can be found in the text by Copeland (2000). Here we simply make the recommendation that all of these solution conditions be optimized in the course of assay development. It is worth noting that there can be differences in optimal conditions for enzyme stability and enzyme activity. For example, the initial velocity may be greatest at 37°C and pH 5.0, but one may find that the enzyme denatures during the course of the assay time under these conditions. In situations like this one must experimentally determine the best compromise between reaction rate and protein stability. Again, a more detailed discussion of this issue, and methods for diagnosing enzyme denaturation during reaction can be found in Copeland (2000). 

Naturally selectivity in a several-component system is primarily influenced by rather strong effects such as the presence or absence of strong H-bonding, but possibly also by much weaker interactions (e.g. of C—H... O type). In this regard, it is interesting to note the similarity between the selectivity exerted by such simple inclusion hosts, e.g. /, and chiral recognition 103). In both cases, weak interactions are of decisive importance in the final outcome of the experiments. Entropic effects have been demonstrated to play a fundamental role in enzymatic reactions 102,107 >. Conceptual similarity of inclusion compounds to more complicated associates is underlined thereby. 

KS Pang, M Rowland. Hepatic clearance of drugs. I. Theoretical considerations of a well-stirred model and a parallel tube model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocellular enzymatic activity on hepatic drug clearance. J Pharmacokin Biopharm 5/6 625-653, 1977. 

---