Inhibition causes

Use of biofilm reactors for ethanol production has been investigated to improve the economics and performance of fermentation processes.8 Immobilisation of microbial cells for fermentation has been developed to eliminate inhibition caused by high concentrations of substrate and product, also to enhance productivity and yield of ethanol. Recent work on ethanol production in an immobilised cell reactor (ICR) showed that production of ethanol using Zymomonas mobilis was doubled.9 The immobilised recombinant Z. mobilis was also successfully used with high concentrations of sugar (12%-15%).10... 

Irreversible metabolic inhibition caused by covalent binding of the inhibitor to the enzyme after being metabolized by the same enzyme. The inhibitory effect remains after elimination of the inhibitor from the body. 

Reversible metabolic inhibition caused by an inhibitor binding to an enzyme site different from the substrate. The degree of inhibition is independent of the substrate concentration. 

Psychostimulants. Figure 2 Dopamine molecules have two different possible targets. Both ways are initially increased by DAT inhibition caused by methylphenidate pre- and postsynaptic dopamine receptors. Stimulation of postsynaptic receptors results in inhibition of presynaptic action potential generation. On the other hand, presynaptic receptor stimulation leads to a transmission inhibition of action potentials. Therefore, both mechanisms are responsible for a decrease in vesicular depletion of dopamine into the synaptic cleft (adapted from [2]). 

The inhibition of brain cholinesterase is a biomarker assay for organophosphorous (OP) and carbamate insecticides (Chapter 10, Section 10.2.4). OPs inhibit the enzyme by forming covalent bonds with a serine residue at the active center. Inhibition is, at best, slowly reversible. The degree of toxic effect depends upon the extent of cholinesterase inhibition caused by one or more OP and/or carbamate insecticides. In the case of OPs administered to vertebrates, a typical scenario is as follows sublethal symptoms begin to appear at 40-50% inhibition of cholinesterase, lethal toxicity above 70% inhibition. 

American pondweed responded to GA3 and the herbicide sulfometuron within 7 days after exposure (Table I). As with terrestial plants, GA3 caused elongation of shoots (internodes) compared to controls, whereas sulfometuron almost completely blocked elongation since no significant lengthening occurred between day 7 and 14. Hie presence of GA3 did not counteract the inhibition caused by sulfometuron. This is reasonable since... 

Determination of the IC50 is a preliminary evaluation of the relative affinity of different compounds for a target enzyme. To evaluate affinity properly, however, one must first define the mechanism of inhibition of the target enzyme by each compound. The next step in the lead evaluation flowchart (Figure 5.1) is to determine if the inhibition caused by a compound is rapidly reversible, slowly reversible, or irreversible. This information will help the investigator understand whether or not the inhibition reaction can be treated as a reversible equilibrium, and thus decide on the best measure of true affinity for a particular compound. 

Carbamates are used as insecticides, nematocides, fungicides, and herbicides the toxicity of carbamate insecticides is similar to that of OP compounds and is based on the inhibition of ACHE. Also, carbamate metabolites may inhibit ACHE but are usually weaker inhibitors than the unchanged compound. Cholinesterase inhibition caused by carbamates is labile, of short duration, and rapidly reversible in fact, the half-life of the inhibited enzymes ranges between some minutes and 2 to 3 hours for RBC-ACHE and is on the order of some minutes for PCHE. Accumulation of cholinesterase activity on repeated exposures, as observed with OP compounds, does not occur with... 

Reversible inhibition caused by materials that can function as ligand. Many compounds will bind to a metal this might be the solvent or impurities in the substrate or the solvent. It can also be a functional group in the substrate or the product, such as a nitrile. Too many ligands bound to the metal complex may lead to inhibition of one of the steps in the catalytic cycle. Likely candidates are formation of the substrate-catalyst complex or the oxidative addition of hydrogen. Removal of the contaminant will usually restore the catalytic activity. 

Scheme 44.2 Catalyst inhibition caused by functional groups in the substrate.

Reversible Inhibition Caused by Materials that can Function as Ligand 1499... 

Catalyst Inhibition Caused by Compounds Containing Heteroatoms... 

Tests are made by examining the inhibition caused by the substance on the sympathomimetic effects of injected adrenaline and of sympathetic nerve stimulation. Among the recently re-oommended anti-adrenaline drugs are iminazole derivatives (e.g. priscol (VIII))2 and / -haloalkylamines (e.g. dibenamine (IX)). The action of dibenamine is almost certainly that of destroying the receptor patches in the effector organ (p. 37). 

The maximum level of HMMA in the urine occurred 72 hours after exposure, which coincides with the time period for maximum urine catecholamine levels. There was a direct relationship between blood cholinesterase inhibition and catecholamine (adrenaline and noradrenaline) levels in the urine and blood (Brzezinski and Ludwicki 1973). Maximum inhibition of cholinesterase activity and maximum plasma catecholamine occurred during the first I-2 hours after exposure. However, catecholamine levels returned to normal more rapidly than cholinesterase activity. It was proposed that high levels of acetylcholine, which are normally associated with cholinesterase activity inhibition, caused a release of catecholamines from the stores in the adrenals. 

Binding of a reversible inhibitor to an enzyme is rapidly reversible and thus bound and unbound enzymes are in equilibrium. Binding of the inhibitor can be to the active site, or to a cofactor, or to some other site on the protein leading to allosteric inhibition of enzyme activity. The degree of inhibition caused by a reversible inhibitor is not time-dependent the final level of inhibition is reached almost instantaneously, on addition of inhibitor to an enzyme or enzyme-substrate mixture. 

A review of the literature (Krishnan and Brodeur 1991) demonstrated that the majority of toxicokinetic interaction results from metabohc induction or inhibition caused by some components of the mixture. These interactions may alter tissue dosimetry and thereby the toxicity of components in the mixture. The tissue doses of chemicals in mixture can be predicted with PBTK models when the binary interactions between aU of the components in the mixture are known (Haddad et al. 1999a,b, 2000a,b). However, the quantitative characteristics of each of these binary interactions have to be determined by experimentation. Given the complexity of the mixtures, to which humans are exposed, this would obviously require an unreahstic large number of experiments in order to characterize the quahtative and quantitative nature of the possible interactions. 

Table 2. Cell growth inhibition caused by different concentration of extractable fluoride according to Gervits [19]...

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