Enzymes toxic

It should be emphasized, however, that this relationship for genetically determined enzyme toxicity has been worked out in detail only with polycyclic hydrocarbon carcinogens. It remains to be determined how many other classes of carcinogens may also show such differences. 

Compound B, a toxicant, is metabolically detoxified. In the presence of an inhibitor of the detoxifying enzymes, there wifi be an increase in toxicity, whereas in the presence of an inducer of these enzymes, toxicity would decrease. 

Noncarcinogenic toxicities are detrimental effects caused by chemicals that do not induce cancer. The most common effects are due to interactions between the chemical and the biological molecules in the receptor, especially enzymes. Toxic chemicals can bind to an important enzyme and reduce or eliminate its function. Some of the most important noncarcinogenic interactions between toxic chemicals and biological molecules include the inhibition of acetylcholinesterase by organophosphate ester and carbamate insecticides, the binding of carbon... 

Biological properties such as the reactivity of enzymes, toxicity or drug action usually involve a combination of fundamental effects that give rise to equations which include more than one parameter. The Hansch equation is usually modified by the addition of terms such as steric parameters ( J or polar substituent constants (a). Examples are found in the catalytic action of a-chymotrypsin on 4-nitrophenyl esters of aliphatic acids (Equation 35). 

The inhibitory potencies of the compounds, along with those of several GAD inhibitors from the literature, are summarized in Table II. Reasonable agreement was found between the bacterial and insect enzymes. Toxic compounds were good inhibitors of GAD, in general, although aminooxy acids 1 and 2 (Table II) were potent inhibitors without being very toxic. A previous observation that insect GAD is not inhibited by aminooxyacetate (15) may be explained by the use of different enzyme preparations in the two studies. In the present work it was found that GAD in a crude muscle homogenate was not consistently inhibited by aminooxyacetate. It was this observation that led to the above purification protocol. 

Enzyme toxic mechanism It suppresses the function of a number of enzymes in the parenchyma organs cells, which ensure oxidation and protein synthesis. 

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. 

Enzymes Toxicity of metals may arise from their actions on enzymes. Many metals may inhibit enzymes by (1) interacting with the SH group of the enzyme (2) displacing an essential metal cofactor of the enzyme, and (3) inhibiting the synthesis of enzyme. 

Peptide enzyme toxicity is related to free radical spin trap reactivity. Neuroreport 6 489-492 Hirano K, Hotta Y, Fujiki K, Kanai A (2000) Corneal amyloidosis caused by Leu518Pro mutation of betaig-h3 gene. Br J Ophthalmol 84 583-585... 

In cases of severe overdose, melia bark or root bark may cause gastrointestinal bleeding, jaundice, hepatomegaly, elevated liver enzymes, toxic hepatitis, visual impairment, and respiratory or circulatory failure (Bensky et al. 2004 Chen and Chen 2004). 

While relatively rare compared with the large number of detoxication reactions performed by Phase I and II enzymes, toxication reactions pose significant risks of chemical disease. In recognition of their potential to increase the risk of cancer. 

Microrganisms are killed in phagocytes by an array of digestive enzymes, toxic oxygen species, and other antimicrobial agents. In addition to internalization... 

Cyanogemc glycosides are potentially toxic because they liberate hydrogen cyanide on enzyme catalyzed or acidic hydrolysis Give a mechanistic explanation for this behavior for the specific cases of... 

As a class of compounds, the two main toxicity concerns for nitriles are acute lethality and osteolathyrsm. A comprehensive review of the toxicity of nitriles, including detailed discussion of biochemical mechanisms of toxicity and stmcture-activity relationships, is available (12). Nitriles vary broadly in their abiUty to cause acute lethaUty and subde differences in stmcture can greatly affect toxic potency. The biochemical basis of their acute toxicity is related to their metaboHsm in the body. Following exposure and absorption, nitriles are metabolized by cytochrome p450 enzymes in the Hver. The metaboHsm involves initial hydrogen abstraction resulting in the formation of a carbon radical, followed by hydroxylation of the carbon radical. MetaboHsm at the carbon atom adjacent (alpha) to the cyano group would yield a cyanohydrin metaboHte, which decomposes readily in the body to produce cyanide. Hydroxylation at other carbon positions in the nitrile does not result in cyanide release. 

The esters of monofluorophosphoric acid are of great interest because of their cholinesterase inhibiting activity which causes them to be highly toxic nerve gases and also gives them medical activity (see Enzyme inhibitors). The most studied is the bis(l-methylethyl)ester of phosphorofluoridic acid also known as diisopropyl phosphorofluoridate [155-91 DFP (5), and as the ophthalmic ointment or solution Isoflurophate USP. It is used as a... 

Phosphonothioate Esters of Phenols. Phosphonates with a single P—C bond are highly toxic and persistent iasecticides but have not been used extensively because some compounds produce delayed neuropathy leading to irreversible paralysis ia higher animals, including humans. Such compounds specifically inhibit an enzyme, neurotoxic esterase, that is responsible for the growth and maintenance of long nerve axons (31,32). 

The development of malathion in 1950 was an important milestone in the emergence of selective insecticides. Malathion is from one-half to one-twentieth as toxic to insects as parathion but is only about one two-hundredths as toxic to mammals. Its worldwide usage in quantities of thousands of metric tons in the home, garden, field, orchard, woodland, on animals, and in pubHc health programs has demonstrated substantial safety coupled with pest control effectiveness. The biochemical basis for the selectivity of malathion is its rapid detoxication in the mammalian Hver, but not in the insect, through the attack of carboxyesterase enzymes on the aUphatic ester moieties of the molecule. 

The biochemical basis for the toxicity of mercury and mercury compounds results from its ability to form covalent bonds readily with sulfur. Prior to reaction with sulfur, however, the mercury must be metabolized to the divalent cation. When the sulfur is in the form of a sulfhydryl (— SH) group, divalent mercury replaces the hydrogen atom to form mercaptides, X—Hg— SR and Hg(SR)2, where X is an electronegative radical and R is protein (36). Sulfhydryl compounds are called mercaptans because of their ability to capture mercury. Even in low concentrations divalent mercury is capable of inactivating sulfhydryl enzymes and thus causes interference with cellular metaboHsm and function (31—34). Mercury also combines with other ligands of physiological importance such as phosphoryl, carboxyl, amide, and amine groups. It is unclear whether these latter interactions contribute to its toxicity (31,36). 

Because of its position in the Periodic Table, molybdenum has sometimes been linked to chromium (see Chromiumand chromium alloys) or to other heavy metals. However, unlike those elements, molybdenum and its compounds have relatively low toxicity, as shown in Table 3. On the other hand, molybdenum has been identified as a micronutrient essential to plant life (11,12) (see Fertilizers), and plays a principal biochemical role in animal health as a constituent of several important enzyme systems (see Mineral nutrients). 

The nephrotoxic amino acid, lyskioalanine [18810-04-3] formed upon alkaline treatment of proteki, was reported ki 1964 (108). Its toxicity seems to be mitigated ki proteki ki that it is not released by normal digestion (109). Naturally occurring new amino acids, which can be classified as protekiaceous or non-protekiaceous, can, as ki the case of those from some legumes, show a remarkable toxicity (110). Eor the details of amino acid toxicity, see reference 6. Enzyme inhibition by amino acids and thek derivatives have been reviewed (111). 

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