Poison enzyme

Ability of oximes to interact directly with some OPC [58] and also with phosphorylated enzyme [59] is considered as an additional protective mechanism of their action. A value of the reaction indicated for the organism depends upon subsequent fate of the phosphorylated oxime. The formation of less toxic products in case of fast degradation of the phosphorylated oxime is evaluated as the process of OPC detoxication [60], while amplification of the poisoning enzyme toxicity is accompanied with the formation of strong phosphorylated oxime [61], That is the reason why prophylactic use of oximes in the last case can result in the reverse effect. 

It should be noted that a number of different enzyme preparations can now be purchased directly from manufacturing chemists. It must be emphasised that the activity of an enzyme, whether purchased or prepared in the laboratory, may vary between rather wide limits. The activity is dependent on the source of the enzyme, the presence of poisons and also on the temperature. It appears, for example, that the quality of horseradish peroxidase depends upon the season of the year at which the root is obtained from the ground. It cannot be expected therefore that all the experiments described below will work always with the precision characteristic of an organic reaction proceeding under accurately known conditions. 

Elucidating Mechanisms for the Inhibition of Enzyme Catalysis An inhibitor interacts with an enzyme in a manner that decreases the enzyme s catalytic efficiency. Examples of inhibitors include some drugs and poisons. Irreversible inhibitors covalently bind to the enzyme s active site, producing a permanent loss in catalytic efficiency even when the inhibitor s concentration is decreased. Reversible inhibitors form noncovalent complexes with the enzyme, thereby causing a temporary de-... 

Mode of Action. All of the insecticidal carbamates are cholinergic, and poisoned insects and mammals exhibit violent convulsions and other neuromuscular disturbances. The insecticides are strong carbamylating inhibitors of acetylcholinesterase and may also have a direct action on the acetylcholine receptors because of their pronounced stmctural resemblance to acetylcholine. The overall mechanism for carbamate interaction with acetylcholinesterase is analogous to the normal three-step hydrolysis of acetylcholine however, is much slower than with the acetylated enzyme. 

Enzymes as Antidotes. Rhodanese [9026-04-4] given along with thiosulfate to counteract cyanide poisoning in mice (224) was the first enzyme used as an antidote. This combination raised the LD q of potassium cyanide in mice by eightfold (224). 

The venoms of poisonous snakes contain (among other things) a class of enzymes known as phospholipases, enzymes that cause the breakdown of phospholipids. For example, the venoms of the eastern diamondback rattlesnake (Crotalus adamanteus) and the Indian cobra Naja naja) both contain phospholipase Ag, which catalyzes the hydrolysis of fatty acids at the C-2 position of glyc-erophospholipids. 

Cells and isolated enzymes are often susceptible to poisoning at low levels of chemical contamination. It is, therefore, necessary to carry out expensive purification of substrates (feedstocks) and water used in bioprocesses. 

Catalase is an important enzyme in cells because hydrogen peroxide is a by-product of metabolism and can poison the cell unless it is decomposed quickly. Hydrogen peroxide is also produced by cells in the immune system, and catalase removes the excess. 

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. 

One form of biological poisoning mirrors the effect of lead on a catalytic converter. The activity of an enzyme is destroyed if an alien substrate attaches too strongly to the enzyme s active site, because then the site is blocked and made unavailable to the true substrate (Fig. 13.42). As a result, the chain of biochemical reactions in the cell stops, and the cell dies. The action of nerve gases is believed to stem from their ability to block the enzyme-controlled reactions that allow impulses to travel through nerves. Arsenic, that favorite of fictional poisoners, acts in a similar way. After ingestion as As(V) in the form of arsenate ions (As043 ), it is reduced to As(III), which binds to enzymes and inhibits their action. 

Zinc and cadmium have an oxidation number of +2 in all their compounds. Zinc is an essential element for human health. It is present in many enzymes and plays a role in the expression of DNA and in growth. Zinc is toxic only in very-high amounts. However, cadmium is a deadly poison that disrupts metabolism by-substituting for other essential metals in the body such as zinc and calcium, leading to soft bones and to kidney and lung disorders. 

Fibrinolytic effecting protease enzyme with glycoprotein structure relative mol mass ca. 30000. Isolation from the poison secretion (venom) of Agkistrodon rhodostoma (malayan pit viper) with chromatographic purification. 

Following inhibition by methyl parathion, acetylcholinesterase activity recovers as a result of the synthesis of new enzyme, generally at a rate of approximately 1% per day. However, the symptoms of methyl parathion poisoning usually resolve much more rapidly. Therefore, even though they are symptom-free, persons poisoned by methyl parathion may be hypersusceptible to its effects and should avoid reexposure for several weeks (Aaron and Howland 1998 Proctor et al. 1988). 

Pawlowska D, Moniuszko-Jakoniuk J, Soltys M. 1985b. The effect of chronic physical exercise on the activity of hydrolytic enzymes in acute poisoning with parathion-methyl in rats. Pol J Pharmacol Pharm 37 639-646. 

CBs, like OPs, act as inhibitors of ChE. They are treated as substrates by the enzyme and carbamylate the serine of the active site (Figure 10.8). Speaking generally, car-bamylated AChE reactivates more rapidly than phosphorylated AChE. After aging has occurred, phosphorylation of the enzyme is effectively irreversible (see Section 10.2.4). Carbamylated AChE reactivates when preparations are diluted with water, a process that is accelerated in the presence of acetylcholine, which competes as a substrate. Thus, the measurement of AChE inhibition is complicated by the fact that reactivation occurs during the course of the assay. Carbamylated AChE is not reactivated by PAM and related compounds that are used as antidotes to OP poisoning (see Box 10.1). 

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