Metabolism detoxification

Table 2. Examples of Metabolic Detoxification and Metabolic Activation of Chemicals by Biological Systems...

Examples of differences in the responses of wildlife organisms to EDCs include the differences in sensitivity to phthalates and bisphenols among mollusks, crustaceans, and amphibians compared to fish. In invertebrates, biological effects are observed at exposures in the ng/L to low pg/L range, compared to high pg/L for most effects in fish (reviewed in Oehtmann et al. 2008). In addition, aquatic mollusks tend to bioconcentrate and bioaccumulate pollutants to a greater level than hsh, possibly owing to poorer capabilities for metabolic detoxification (see Chapter 4, Section 4.3). 

As illustrated in Table 43-5, the discovery of the nuclear receptor superfamily has led to an important understanding of how a variety of metabolites and xenobi-otics regulate gene expression and thus the metabolism, detoxification, and elimination of normal body products and exogenous agents such as pharmaceuticals. Not surprisingly, this area is a fertile field for investigation of new therapeutic interventions. 

Synthesis of tatty acids, cholesterol, and other steroids, metabolic detoxification of drugs, poisons, end NHa... 

Methylphenanthrene fulfills the structural requirements but, as in the case of the other monomethylphenanthracenes, is inactive as a tumor initiator on mouse skin ( 5). This seems to be due to facile metabolic detoxification by formation of the 9,10-dihydrodiol, a process which is blocked in the tumorigenic isomers 1,4- and 4,10-dime thy lphenanthrene ( 5,j>). Among the methylated benzoicIphenan-threnes, the 3-,4-,5-, and 6-methyl isomers are the most tumori-genic The 1-methyl isomer, in which the methyl group is present in a 4-sided "fjord , is only weakly active like the parent hydrocarbon (23). 

Zinedine A, Soriano JM, Molto JC, Jordi Manes J (2007) Review on the toxicity, occurrence, metabolism, detoxification, regulations and intake of zearalenone an oestrogenic mycotoxin. Food Chem Toxicol 45 1-18... 

MFO). Similar MFO microsomal redox systems operate for the metabolic detoxification of drugs and some waste products (Section 6.4). 

Using pig and human microsomes and cDNA-expressed human flavin-containing monooxygenase, Lin and Cashman demonstrated a metabolic detoxification pathway that converts tyramine into the HA derivative, 20, and the anti oxime, 21, which was sufficiently stable to permit its chemical characterization". ... 

Metabolic Detoxification of Linear and Angular Furanocoumarins by Caterpillars of the Black Swallowtail Butterfly... 

Our studies indicate that rapid metabolic detoxification of linear furanocoumarins is an effective resistance mechanism for K polyxenes against the toxic effects of these compounds. It has been postulated that the adaptation of some plants to produce angular furanocoumarins was in response to the reduced effectiveness of the linear furanocoumarins as deterrents for herbivores such as polyxenes (22). Such may Indeed be true, but our studies on the comparative detoxification of linear and angular furanocoumarins suggest that, at best, the presence of angular furanocoumarins in plants confers only a tenuous margin of relative "safety" against polyxenes. 

Ring substitution leading to an attenuation of metabolic detoxification... 

This characteristic, however, is not universally found in all triazine-resistant weeds. Gray et al. (1995a, b) found that velvetleaf resistance to atrazine in Wisconsin was not associated with a reduction in fitness, productivity, or intraspecific competitive ability. This triazine-resistant species found in Maryland and Wisconsin does not have D1 level resistance in the chloroplasts, but instead has a more rapid metabolic detoxification of triazines in these biotypes. The extent of the rapid metabolic resistance in other velvetleaf-resistant biotypes is unknown. 

We have not pursued mechanisms but suggest that the enhancement of carcinogenesis may be related to a role for riboflavin in the activation of enzymatic processes involved with metabolic detoxification of MBN, similar to azo reductase and its role in the detoxification of 4-dimethylaminoazobenzene (32). In this case riboflavin activates azo reductase in the liver and this, in turn, is associated with decreased carcinogenicity. Conversely, when animals are deprived of riboflavin, there is less active enzyme present to detoxify the chemical and the induction of liver cancer is enhanced. A similar process may be functioning in our MBN, riboflavin deprived model but the exact nature of the mechanism requires additional research. 

Most proteomics analyses involve 2-D electrophoresis and MALDl-TOF MS steps, as this approach allows for a reliable quantification of changes in protein levels. In one study, the LC-MS/MS approach was used for the detection of proteins enriched in amyloid plaques in the AD brain (liao et al., 2004). Employing the former proteomic approach, levels of about 100 proteins were foimd to be changed in the AD brain and cerebrospinal fluid (CSF) in comparison with the control brain and CSF, respectively (Table 15.1). These proteins have various functions, mainly involved in neurotransmission, guidance, signal transduction, metabolism, detoxification, and conformational changes. The CSF proteins are plasma proteins. 

Ivie, G.W., Bull, D.L., Beier, R.C., Pryor, N.W., and Oertli, E.H., Metabolic detoxification Mechanism of insect resistance to plant psoralens, Science, 221, 374,1983. 

In some cases, increased toxicity of insecticides can be attributed to materials that enhance cuticular penetration of the insecticides without involving inhibition of metabolic detoxification. For example, Sun and Johnson (1972) found that carbaryl was more toxic to houseflies when topically applied in kerosene than in acetone. These authors classified this type of synergism as quasi-synergism. 

The challenge here is to find suitable inhibitors at the enzyme level that retain this activity at the whole-plant level. In addition, this approach is only feasible when resistance is conferred by target site mutations if resistance were conferred also by metabolic detoxification an additional set of screens against detoxifying enzymes would have to be included. 

In addition, due to the reversibility of the binding reaction of sarin and soman to CarbE, it appears that CarbEs are involved in metabolic detoxification of these agents to their corresponding nontoxic metabolites isopropyl methylphosphonic acid (IMPA) and pinacolyl methylphosphonic acid (PMPA) (Jokanovic et al, 1996). 

FIGURE 52.1. Metabolic detoxification of warfare nerve agents tabun, sarin, soman, and VX in mammals in vivo. Chemical names of metabolites are EDMPA - ethyl dimethylaminophosphoric acid, IMPA - isopropyl methylphosphonic acid, PMPA - pinacolyl methyl-phosphonic acid, EMPA - ethyl methylphosphonic acid, and MPA - methylphosphonic acid. 

Is bioavailability, metabolism, detoxification, elimination likely to be an issue ... 

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