Enzyme poisoning

FIGURE 13.42 (a) An enzyme poison (represented by the blue sphere) can act by attaching so strongly to the active site that it blocks the site, thereby taking the enzyme out of action, (b) Alternatively, the poison molecule may attach elsewhere, so distorting the enzyme molecule and its active site that the substrate no longer fits. 

Vesicular compartment control over export, exocytosis, of enzymes, poisons... 

It seems established that galactose-l-phosphate is an enzyme poison, blocking the cell s most important source of energy. The failure to thrive characteristic of galactosemia is thus explained the less severely affected infants were possibly exposed to lower concentrations of galactose-l-phosphate, either because of their diet or because of some peculiarity of constitution. 

Any compound which reduces the activity of an enzyme is an inhibitor. Such compounds may be endogenous or exogenous (i.e. drugs or toxins) and the impact on the enzyme may be a temporary or permanent effect. Temporary or reversible inhibitors are important in metabolic control whereas permanent or irreversible inhibitors are in effect enzyme poisons. 

Inhibitors may act reversibly or irreversibly to limit the activity of the enzyme. Irreversible inhibitors are enzyme poisons and indeed many of them are poisonous in the common sense of the word cyanide for example, is an irreversible inhibitor of one of the cytochromes in oxidative phosphorylation. 

Many other compounds have been included in studies on sucrose response. Most of these have been herbicides or enzyme poisons. None of the common herbicides had any positive effect on sucrose at rates up to that causing severe foliar injury. Earlier reports of response from 2-(2,4,5-trichlorophenoxy)propionic acid and 2,2-dichloropropionic acid could not be substantiated in British Guiana and Queensland. 27 Some compounds, such as 3-(p-chlorophenyl)-l,l-dimethylurea (monuron), (2,4-dichloro-phenoxy) acetic acid in soil, ethylenediaminetetraacetic acid, and leaf desiccants decreased sucrose and juice solids content. 20 Field trials with several chemicals in Trinidad showed enhanced sucrose at 14 to 28 days before harvest resulting from the application of 8 and 12 lb. (per acre) of... 

Enzyme poisons have been studied mainly in attempts to understand the normal physiological processes. As would be expected, synthesis and accumulation of sucrose have often been drastically lowered. In particular, the inhibition of the formation of D-fructose diphosphate and the conversion of D-glucose into D-fructose inhibited the formation of sucrose.288 330... 

Propenaldehyde. Aldehyde group. Typically available as a 92% active, liquid. It is flammable, volatile, lachrymatory, and a strong irritant. Acrolein is a protein and enzyme poison. It is stabilized against polymerization by the addition of hydroquinone (oxidation results in polymerization, rendering acrolein inactive as a microbiocide). Although only small dose levels are required (1.5 to 3.0 ppm) to achieve threshold toxicity, rapid microbial resistance can occur. This product is seldom used today as the effort is often not worth the gain. 

Alpha-amylase is most active at its pH optimum of 6.3 to 6.8.108,109 It is inactive at pH values below 4 and above 9. Enzymic starch conversion is terminated by raising the temperature until enzyme denaturation occurs or by the addition of enzyme poisons, such as the ions of copper, mercury or zinc. Inactivation can also be achieved by moving the pH outside the enzyme s active limits or by the addition of oxidizing agents, such as sodium hypochlorite, hydrogen peroxide or barium peroxide. 

Undesirable deactivation may be caused by high temperature and time, for example, caused by transport and storage and also by enzyme poisons such as certain surfactants (especially cationic ones), formaldehyde-containing products or heavy metal ions. An activation effect on cellulases was reported by Nicolai and co-workers. Alkaline pretreatment, low concentrations of selected non-ionic surfactants, polycarboxylic acids and polyvinyl pyrrolidone can enhance the bio-fmishing of cellulosics. 

The salts of heavy metals, namely iron and copper salts, are general enzyme poisons and protein coagulants. Iron sulfate causes plasmolysis, though Aberg (1948), on killing Sinapis plants with 5% iron sulfate solution, found no plasmolysis in the plants or damage to the chloroplasts. 

As the inorganic phosphate content of the blood drops during absorption of these sugars, there is a theory that the specific-rate absorption of glucose, galactose, and fructose involves a temporary combination with phosphate. The hypothesis is supported, though not proved, by the fact that several enzyme poisons can lower the rate of absorption of these sugars (69). 

The first major division of inhibitors is into two large groups of compounds irreversible and reversible inhibitors. Irreversible inhibitors are enzyme poisons, often chemically reactive compounds, which enter into chemical reactions with enz5nnes, forming irreversibly covalent bonds with the enzyme and reducing its activity to zero. An enzyme inactivated by an irreversible inhibitor caimot be reactivated by dialysis or a similar mild physical procedure. Many enzymes are poisoned by trace amounts of heavy metal ions this type of inhibition can be, in principle, reversed by dialysis against chelators such as EDTA or histidine. 

If a protein recognizes and binds the transition state for a reaction, then that reaction will be accelerated by catalysis. This is because a reaction will go faster if it becomes easier to reach the transition state, which will be the case if the transition state is stabilized more than is the substrate (note how TS is stabilized in this way in Fig. 16.1). An enzyme that hydrolyzes an ester RCOOMe as substrate may well recognize the transition state 16.2 for the attack of water on the ester. Such an enzyme may bind a transition state analogue, such as the phosphate 16.3 much more tightly than it binds the starting ester RCOOMe and inhibit the enzyme (poison the catalyst). 

Somers, G.F. The influence of light, temperature, and some enzyme poisons upon the total organic aci= content of leaf tissue of Kalanchoe daigremontiana Hamet et Perrier. Plant Physiol. 26,1-18 (1951)... 

This relationship is sometimes obscured by the interaction of other factors (Barker and Mapson, 1952), and such evidence implies that the connection between these two substances is not direct. A connection between the level of sucrose and ascorbic acid has also been emphasized in experiments in which detached leaves have been treated with several enzymic poisons (Mapson and Barker, 1948). Ascorbic acid disappears from detached leaves when these are supplied with solutions of iodoacetate, fluoride, or arsenite. In each case the disappearance of ascorbic acid was preceded by a parallel fall of sucrose. It is clearly too soon to speculate... 

It therefore appears reasonable to state that there is an incontrovertible relationship between the deposition of excess copper stores and the development of structural and fimctional defects in certain tissues. This sequence of events can be reversed by the establishment of a negative copper balance with chelating agents. As copper is an enzyme poison there seems little doubt that the metal must be implicated in the pathological changes observed. Now since it has been demonstrated that, in Wilson s disease, copper accumulates in the brain 2ind liver in concentrations sufficient to inhibit essential enzymes, then it must be asked how 2ind why this... 

Copper, as has already been discussed, is an enzyme poison and the sulphydryl-dependent enzymes are probably those most vulnerable to attack. 

Inhibitor substances which often act as enzyme poisons and are chemically different from the permeant may reduce the rate of penetration. Different inhibitors will "poison" various facilitated diffusion systems specifically. This criterion also applies to active transport systems. 

The study of the inhibitors of enz3rmes has also contributed to our understanding of how enzymes act. Certain enzyme poisons such as carbon monoxide, cyanide and diethyl dithiocarbamate have been shown to inactivate enz)rmes by virtue of their high affinity for metals. Thus the inhibition of cytochrome oxidase by CO and CN is because these combine with the iron of the haem prosthetic group. Similarly, it is the affinity of dithiocarbamate for copper which makes... 

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