Detoxification conjugation

Cytotoxic activity. Water extract of the dried root, in cell culture, was inactive on CA-9KB, ED50greater than 0.1 pg/mL The methanol extract was active on Leuk-P388, ED50 0.57 pg/mL L Detoxification activity. Phenolic resin, in increasing levels, was mixed with alfalfa pellets and fed to wood rats. Three detoxification pathways and urine pH, which are related to detoxification of allelochemicals, were measured. The excretion rate of two-phase II detoxification conjugates, glucu-... 

While not aU foreign compoimds contain nitrogen, the majority of pharmacenticals do but as they me ingested in small doses, their contribution to nitrogen excretion is minor. There me essentially four processes of detoxification conjugation, oxidation, reduction, and hydrolysis, and more than one process may occm with any pmticnlm foreign componnd. 

Herbicide selectivity in crops may involve a three-step process of detoxification, conjugation and transport into the vacuole. These three processes can be induced in a coordinated fashion by safeners. The major detoxifying enzymes occur in large gene families, which results in considerable variation in selectivity patterns. Our understanding of these enzymes and their regulation has been greatly assisted by new molecular techniques. 

MDR-ABC Transporters. Figure 3 Detoxification cellular mechanisms. X, toxic compound X-OH, oxidized toxic compound GS-X, conjugated toxic compound OATP, organic anion transporting proteins CYPs, cytochromes GSH, glutathion UDPGIcUA, Uridine 5-diphosphoglucuronic acid PAPs, 3-phosphoadenylylsulfate. 

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. 

Initially formed polar metabolites such as phenols and amines may be conjugated to water-soluble terminal metabolites that are excreted into the medium and function as an effective mechanism of detoxification. For example, pentachlorophenol and pentachlorothiophenol produced from pentachloronitrobenzene conjugated represented the major metabolites. Although the naphthalene dihydrodiol was the major metabolite produced from naphthalene, the further transformation... 

Jakokby, W.B. (1981). Detoxification and drug metabolism conjugation and related systems. In Methods in Enzymology, Vol. 77. Academic Press, New York... 

One of the most important functions of GSTs is the detoxification of endogenous as well as exogenous substances via conjugation with glutathione... 

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. 

Detoxification pathways (oxidation/reduction/hydrolysis/conjugation) Toxification pathways (oxidation/reduction/hydrolysis/conjugation)... 

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. 

Fig. 8. Initial detoxification of Metamitron, 2,4-D, and Malathion by deamination, ether cleavage, and conjugation, respectively...

Together with glutathione conjugation, hydration is a major pathway in the inactivation and detoxification of arene oxides. Exceptions to this rule will be treated when discussing polycyclic aromatic hydrocarbons. Arene oxides are good substrates for microsomal EH, as evidenced in Table 10.1, where hydration of selected arene oxides, alkene oxides, and cy-cloalkene oxides by purified rat liver epoxide hydrolase is compared. The hy- ... 

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