Big Chemical Encyclopedia

Chemical substances, components, reactions, process design ...

Articles Figures Tables About

Synthesis, lethal

The name lethal synthesis was devised by Peters to describe the biochemical alteration of fluoroacetic acid, which is not toxic in itself but is built up by [Pg.580]

What distinguishes lethal synthesis from the cases of degradation before action discussed in Section 3.6 is simply that it is synthesis and not degradation a substance with only two carbon atoms has been made into one with six. Moreover, the raw material for this synthesis passes through at least three enzyme systems, and is changed a little by each, before it becomes toxic. [Pg.581]

Fluoroacetic acid occurs in a South African plant Dkhapetalum, and has killed many cattle in that country. The toxic action of fluoroacetic acid does not depend on any chemical reactivity on the part of fluorine, but on the small size of the fluorine atom (Table 9.1) (Bartlett and Barron, 1947), which deceives the earlier, poorly discriminating enzymes into treating it as a hydrogen atom whereas the later enzymes have more inbuilt precision. Fluoroacetic acid, which is used to exterminate rabbits in their burrows, is not very selective and presents a hazard to human beings. [Pg.581]

Carcinogens are counter-selective chemicals, often harmless in themselves, which the host s metabolism can elaborate into the true carcinogenic agents. The first link between cancer and the chemical environment occurred in 1775, when Potts traced the frequent scrotal cancers of young chimney-sweeps to contact with tar and soot (the lads were commonly stripped of their clothes and impelled up the flues). A century and a half passed before the causative chemical was isolated from coal tar and found to be benzo[ z]pyrene (13.50) (Cook, Hewett and Hieger, 1933). [Pg.581]

Until that time, it had been assumed that cancers were the inevitable accompaniment of ageing. Today, because of the results of comparative studies of populations, the triggering of cancer is seen to be largely environmental. This follows from the great variation in the amount and types of cancer found in different communities in different parts of the world. The manifestations of cancer in migrants, too, changes in proportion as they adapt their life-style to the country of adoption. The International Agency for Research on Cancer (1976) reported that 80% or more of all human cases are activated by exposure [Pg.581]


Lethal Synthesis. This is a process in which the toxic substance has a close stmctural similarity to normal substrates in biochemical reactions. As a result, the material may be incorporated into the biochemical pathway and metabolized to an abnormal and toxic product. A classic example is... [Pg.228]

Peters, Sir R. A. (1954). Biochemical light upon an ancient poison a lethal synthesis. Endeavour, SI, 115. [Pg.231]

The key to unraveling the toxicity of fluoracetate came from observations of Buffa and Peters (1949) that in animals treated with FAc, considerable quantities of citrate accumulated in some tissues. Oxygen uptake was also diminished. The citric acid cycle was thus implicated as the site of inhibition. Fluorcitrate was then isolated from the affected tissues. It was found to be a powerful competitive inhibitor of aconitase, thus blocking citrate oxidation. The suggestion was therefore made that fluoracetate was toxic not in itself, but because it was metabolized in cells via fluoracetyl CoA to give a toxic derivative, an example of lethal synthesis —the capacity of organisms to metabolize nontoxic compounds and convert them to potentially lethal products. [Pg.80]

Peters, R.A. (1963). Biochemical Lesions and Lethal Synthesis. Pergamon Press, Oxford. [Pg.99]

Occasionally, hepatic metabolism of a compound creates a metabolite which is more toxic than the parent this is called a lethal synthesis. An example is given in the following section. [Pg.204]

With a few notable exceptions—such as puromycin and its relatives, psicofuranine and decoynine, and certain 9-alkylpurines-which will be discussed later, purines and their nucleosides must be anabolized to nucleoside phosphates in order to exert their biological effects. This type of metabolic event has been called a lethal synthesis , because it results in the death of cells that carry it out. [Pg.70]

Fluoroacetate undergoes a "lethal synthesis"(18) to 2-fluorocitrate which may reversibly inhibit aconitase and which irreversibly binds to a membrane-associated citrate transport protein(19,20). Insecticidal and other biocidal uses of fluoroacetate (or its metabolic precursors) received considerable attention twenty-five years ago( ) but most uses have been abandoned due to high nonspecific vertebrate toxicity of these compounds. Vfe have reported the use of o)-fluoro fatty acids and their derivatives as delayed-action toxicants for targeted... [Pg.136]

Phytosterol dealkylation can be harnessed in insects to release a fluoroacetate equivalent from a 29-fluorinated sterol. Moreover, the fluorocitrate which then results from the "lethal synthesis" can be isolated and chemically characterized. hope that the range of insects susceptible to the 29-fluorophytosterols and more commercially viable analogs will be further explored. Furthermore, we urge wider scrutiny of insect biochemical pathways in search of possible targets for suicide substrates or latent toxin release. [Pg.140]

Purine Antimetabolites. Purine synthesis can be blocked by 6-mercaptopurine (7.77) and 6-thioguanine (7.78). Both require conversion to the mononucleotide in a lethal synthesis —a mechanism distinguished from the formation of suicide substrates in that the enzyme that transforms the inactive pro-dmg to the active inhibitor is different from the enzyme that is being blocked. inhibitors are formed and bound by the same... [Pg.450]

BIOCHEMICAL EFFECTS LETHAL SYNTHESIS AND INCORPORATION 7.8.1 Fluoroacetate... [Pg.358]

Monofluoroacetic acid (fluoroacetate) (Fig. 7.61) is a compound found naturally in certain South African plants, which causes severe toxicity in animals eating such plants. The compound has also been used as a rodenticide. The toxicity of fluoroacetate was one of the first to be studied at a basic biochemical level, and Peters coined the term "lethal synthesis" to describe this biochemical lesion. [Pg.358]

Among the most deadly of simple compounds is sodium fluoroacetate. The LD50 (the dose lethal for 50% of animals receiving it) is only 0.2 mg/kg for rats, over tenfold less than that of the nerve poison diisopropylphosphofluoridate (Chapter 12).a b Popular, but controversial, as the rodent poison "1080," fluoroacetate is also found in the leaves of several poisonous plants in Africa, Australia, and South America. Surprisingly, difluoroacetate HCF2-COO is nontoxic and biochemical studies reveal that monofluoroacetate has no toxic effect on cells until it is converted metabolically in a "lethal synthesis" to 2R,3R-2-fluorocitrate, which is a competitive inhibitor of aconitase (aconitate hydratase, Eq. 13-17).b This fact was difficult to understand since citrate formed by the reaction of fluorooxalo-acetate and acetyl-CoA has only weak inhibitory activity toward the same enzyme. Yet, it is the fluorocitrate formed from fluorooxaloacetate that contains a fluorine atom at a site that is attacked by aconitase in the citric acid cycle. [Pg.957]

Lethal synthesis can also be used to obtain DHFR- cells by incubating in the presence of 6[3H]deoxyuridine. In the presence of DHFR and thymidylate synthetase this is converted into [3H]thymidine and [3H]DNA which results in cell death. [Pg.266]


See other pages where Synthesis, lethal is mentioned: [Pg.289]    [Pg.1011]    [Pg.1014]    [Pg.102]    [Pg.236]    [Pg.517]    [Pg.196]    [Pg.80]    [Pg.87]    [Pg.122]    [Pg.398]    [Pg.406]    [Pg.938]    [Pg.957]    [Pg.957]    [Pg.1011]    [Pg.1014]    [Pg.289]    [Pg.534]    [Pg.19]    [Pg.350]   
See also in sourсe #XX -- [ Pg.1011 ]

See also in sourсe #XX -- [ Pg.80 ]

See also in sourсe #XX -- [ Pg.231 ]

See also in sourсe #XX -- [ Pg.1011 ]

See also in sourсe #XX -- [ Pg.534 ]

See also in sourсe #XX -- [ Pg.1011 ]

See also in sourсe #XX -- [ Pg.123 ]

See also in sourсe #XX -- [ Pg.798 , Pg.800 ]

See also in sourсe #XX -- [ Pg.124 , Pg.128 ]

See also in sourсe #XX -- [ Pg.580 ]

See also in sourсe #XX -- [ Pg.30 , Pg.34 , Pg.35 ]

See also in sourсe #XX -- [ Pg.139 , Pg.141 ]

See also in sourсe #XX -- [ Pg.194 ]

See also in sourсe #XX -- [ Pg.469 ]




SEARCH



Biochemical effects lethal synthesis and incorporation

Enzyme synthesis of lethal substance

Fluoroacetate, lethal synthesis

Fluorocitrate, lethal synthesis

Lethality

Purines lethal synthesis

© 2024 chempedia.info