Detoxication reductive metabolism

Induction of P-450 Metabolism and Isoenzymes. When organisms are exposed to certain xenobiotics their ability to metabolize a variety of chemicals is increased. This phenomenon can produce either a transitory reduction in the toxicity of a drug or an increase (if the metabolite is the more toxic species). However, this may not be the case with compounds that require metabolic activation. The exact toxicological outcome of such increased metabolism is dependent on the specific xenobiotic and its specific metabolic pathway. Since the outcome of a xenobiotic exposure can depend on the balance between those reactions that represent detoxication and those... 

Reactions of biotransformation of xenobiotics are usually divided into Phase I and Phase II reactions. In Phase I reactions a polar group, such as hydroxyl (-OH), carboxyl (-COOH), thiol (-SH) and amino (-NH2) group, is introduced into the molecule through the reactions of oxidation, reduction and hydrolysis. Metabolites formed can be more toxic than parent compounds (i.e. paraoxon compared to parathion), but some other nontoxic metabolites can be formed as well. In Phase II reactions polar metabolites are conjugated with endogenous substrates such as glucuronides, sulfates, acetates and amino acids, which form hydrosoluble products that can be readily excreted in urine. However, in the case of OPC it is acceptable to divide reactions of biotransformation to activation and detoxication processes. In these metabolic processes significant role have diflerent enzyme... 

More often than not, these metabolic processes are detoxication reactions. However, there arc some cases in which metabolism through cither phase I or phase II can make the chemical more reactive than the parent compound. As will be shown later, thi.s is particularly true in the case of OP compounds, in which the conversion of a P—S moiety to a P=0 group can result in increa.sing toxicity substantially. Usually, however, metabolic events that increase the water solubility of a chemical cause. significant reductions in its biological half-life by making it more readily excreted. 

Parathion, paraoxon and EPN are subject to reduction of the aromatic nitro group to an amino group [159] by mammalian, avian and piscine tissues [160], Paraoxon is the most readily reduced of the three compounds, EPN the least. Paraoxon metabolism to aminoparaoxon is the route of inactivation by rat, chicken and guinea-pig livers in vitro [160]. However, enzymatic hydrolysis of the phosphorus-nitrophenyl linkage of the oxo-analogues appears to he a major pathway of detoxication in manunals [142, 161, 162] but bovine rumen fluid is capable of reducing parathion and EPN to their... 

Now for a third LKF One of the most actively metabolized plant lipids on earth Is an arsenic compound In most of the ocean s surface water, phosphate concentrations are so reduced that the ubiquitous Isomorphous Ion, arsenate, can exceed It In concentration. Algae absorb arsenate In their quest for phosphate and so must detoxicate It Immediately or die. Phosphorous and arsenic differ In that phosphate esters are relatively stable compared to arsenate esters. Further, phosphate Is not reduced by metabolic reductants while arsenate and arsenlte are readily reduced to yet more toxic forms (Knowles and Benson, 1983 Knowles, 1982) which bind sulf-hydryl groups. In Its effort to release Its critical sulfhydryl enzymes from their arsenic bondage the arsenic Is freed as a methylated and 5-deoxyrlbosylated trlalkylarslne oxide Identified by Edmonds and Frances-conl (1981 Edmonds et al., 1982),... 

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