Detoxification mechanisms

There is a second type of cholinesterase called butyrylcholinesterase, pseudocholinesterase, or cholinesterase. This enzyme is present in some nonneural cells in the central and peripheral nervous systems as well as in plasma and serum, the liver, and other organs. Its physiologic function is not known, but is hypothesized to be the hydrolysis of esters ingested from plants (Lefkowitz et al. 1996). Plasma cholinesterases are also inhibited by organophosphate compounds through irreversible binding this binding can act as a detoxification mechanism as it affords some protection to acetylcholinesterase in the nervous system (Parkinson 1996 Taylor 1996). 

Conjugation of polar groups such as amines, carboxylic acids, and phenolic hydroxyl gronps produce water-soluble compounds that are excreted and these reactions therefore fnnction as a detoxification mechanism. 

Igarashi H, Fujino T, Zhu Y, Uchida H, Watanabe M. 2001. CO tolerance of Pt alloy electrocatalysts for polymer electrolyte fuel cells and the detoxification mechanism. Phys Chem Chem Phys 3 306-314. 

El Saidy, M.F., M. Auda, and D. Degheele. 1989. Detoxification mechanisms of diflubenzuron and tefluben-zuron in the larvae of Spodoptera littoralis (Boisd.). Pestic. Biochem. Physiol. 35 211-222. 

Biomethylation is the preferred detoxification mechanism for inorganic arsenicals. 

GSTs contain a site that accommodates GSH ("GSH binding domain") [31], where the proton of the GSH s thiol group is abstracted, promoting the nucleophilic conjugation of the thiolate to electrophilic substrates. The resulting adducts become more water-soluble and are then eliminated by a phase II detoxification mechanism. 

Spahn-Langguth H, Benet LZ. Acyl glucuronides revisited is the glucuronidation process a toxification as well as a detoxification mechanism. Drug Metab Rev 1992 24 5-47. 

In a simplified model, the metal ions equilibrate on the outside of the cell with biologically produced and excreted ligands l 2 or ligands on the cell surface L3 these reactions are followed by a slow transport step to the inside of the cell. In the cell, the metal ions may be used in biochemical processes or become trapped in inactive forms as a detoxification mechanism. (After Williams, 1983) (cf. Fig. 4.15a). (From Sigg, 1987)... 

Glickman et al. have also reported that PCP-glucuronide is excreted in the bile of rainbow trout exposed to PCP and penta-chloroanisole media(7). The biliary excretion after glucuronide conjugation must be one of general detoxification mechanisms for PCP in fish. 

H. Spahn-Langguth, L. Z. Benet, Acyl Glucuronides Revisited Is the Glucuronidation Process a Toxification as well as a Detoxification Mechanism , Drug Metab. Rev. 1992, 24, 5 - 48. 

Acute poisoning only occurs when the detoxification mechanism is overwhelmed. This reaction is enhanced by giving sodium thiosulfate and sodium nitrate intravenously as 20% solutions in a 3 1 ratio, which is a recommended antidote for acute cyanide poisoning. It is the thiocyanate metabolite that causes chronic disease when cyanide forage is ingested over an extended period. 

There is no information on the metabolism of 3,3 -dichlorobenzidine in children. Limited data in humans suggest that N-acetylation is an important metabolic pathway (Belman et al. 1968), and a detoxification mechanism. N-Acetylation in humans is likely done by one of two families of N-acetyltransferases. One of these families, NAT2, is developmentally regulated (Leeder and Kearns 1997). Some enzyme activity can be detected in the fetus by the end of the first trimester. Almost all infants exhibit the slow acetylator phenotype between birth and 2 months of age. The adult phenotype distribution is reached by the age of 4-6 months, whereas adult activity is found by approximately 1-3 years of age. Also, UDP-glucurono-syltransferase, responsible for the formation of glucuronide conjugates, seems to achieve adult activity by 618 months of age (Leeder and Kearns 1997). These data suggest that metabolism of 3,3 -dichloro-benzidine by infants will differ from that in adults in extent, rate, or both. 

Since the majority of an oral dose of histamine is excreted as various histamine metabolites, the metabolism of histamine probably serves as a detoxification mechanism. As noted earlier, the small intestine and liver are particularly active in histamine metabolism and would be expected to protect against the toxicity of orally administered histamine. 

Bagchi and Kleiner suggested that endogenous HA can undergo dismutation by the action of a cyanobacterial hydroxylamine dismutase, thereby providing a detoxification mechanism for excess hydrogen peroxide, as well as for an excess of HA itself. This... 

This study showed that hydroquinone was glycosated by the barley to form arbutln and was therefore effectively detoxified. If the equilibrium of the detoxification mechanism of a plant is sensitive to an oversupply of the toxic and detoxified compound, an oversupply of a detoxified compound could produce equilibrium amounts of the toxic compound. Cell culture bloassay (Table II) showed that hydroquinone is not significantly detoxified in vivo in leafy spurge, indicating the succeptiblllty of the plant to low levels of hydroquinone which could originate from an oversupply of arbutln. The observed toxicity of -benzoquinone in the cell cultures and seed bloassays also indicates that oxidation processes affecting hydroquinone will not detoxify the compound vivo. 

It is possible that these ecoregulatory enzymes, used by the insect to inhibit targeted plant toxlficatlon systems, may themselves be the principal target of the production of tannins by plants. The discovery of other examples of secondary chemical interactions with enzymes dedicated to the regulation of toxifica-tion and detoxification mechanisms may be expected as our knowledge of chemically mediated plant-insect interaction expands. 

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