Organic xenobiotics Biotransformation

Virtually all organisms possess biotransformation or detoxification enzymes that convert lipophilic xenobiotics to water-soluble and excretable metabolites (Yu et al. 1995). In the metabolic process, PAHs are altered by Phase I metabolism into various products such as epoxides, phenols,... 

A schematic representation of the possible molecular fate and effects of organic xenobiotics taken up into animals is given in Fig. 1. It shows the relationship between the biotransformation pathways involved in the detoxication and removal of xenobiotics and those involved in the generation of toxic molecular species. It identifies four potential sources of toxic molecular species derived either directly or indirectly from the presence of the organic xenobiotic, viz. the parent compound itself, reactive metabolites and free radical derivatives of the compound, and enhanced production of toxic oxygen species (oxyradicals). The scheme and the details of the reactions and enzymes involved (Table 1-3) are based largely on mammalian and other vertebrate studies. 

Fig. 1. Schematic representation of the major pathways of biotransformation, detoxication and toxication, and the resultant molecular effects, of organic xenobiotics in animals. —toxic molecular effects. See text and Tables 1 to 3 for further details...

D. R. Livingstone, The fate of organic xenobiotics in aquatic ecosystems quantitative and qualitative differences in biotransformation by invertebrates and fish. Comp. Biochem. Physiolo., Part A, 1998, 120, 43-49. 

Most living beings have the capacity to metabolize xenobiotics by the process denominated biotransformation (Tuvikene, 1995). Biotransformation is characterized as a conjunct of enzymatic reactions, responsible for the conversion of the liposoluble substances in hydrosoluble facilitating, thus, their excretion process. However, although the purpose of the xenobiotics biotransformation is detoxification not always the originated metabohte is less toxic than the own chemical. Thus, xenobiotics biotransformation can increase the toxicity of the chemical products by the formation of electrophilic metabolites, extremely reactive, which can present potential to bind, covalently, with macromolecules inside the cells with DNA, RNA and proteins, which can result in several alterations such as disturbance in the immime system, mutations and even the organism death (Stanley, 1992,1994 Landis and Yu, 1998 Guecheva and Henriques, 2003). 

These procedures may clearly result in the dominance of organisms that carry out only biotransformation of the xenobiotic, although the biodegradation of many of these compounds has also been demonstrated using the same or other organisms. 

These results may be viewed in the wider context of interactions between potential ligands of multifunctional xenobiotics and metal cations in aquatic environments and the subtle effects of the oxidation level of cations such as Fe. The Fe status of a bacterial culture has an important influence on synthesis of the redox systems of the cell since many of the electron transport proteins contain Fe. This is not generally evaluated systematically, although the degradation of tetrachloromethane by a strain of Pseudomonas sp. under denitrifying conditions clearly illustrated the adverse effect of Fe on the biotransformation of the substrate (Lewis and Crawford 1993 Tatara et al. 1993). This possibility should therefore be taken into account in the application of such organisms to bioremediation programs. 

Comparative Metabolism. Since the liver is the major organ involved in the biotransformation of xenobiotics, primary hepatocyte cultures provide an excellent model for in vitro metabolism studies. Primary hepatocyte cultures provide useful tools with which to study the comparative metabolism of xenobiotics by both humans and laboratory animals. 

The formation of polar metabolites from nonpolar materials may actually facilitate monitoring programs—in many cases the polar chemicals are highly concentrated in certain body fluids such as bile and urine. On the other hand, materials such as certain cyclodienes and polychlorinated biphenyls, which are very lipid soluble and resistant to metabolism, may accumulate and these chemicals may persist in the environment and may be transferred via the food chain to man. There is also interest in these biotransformation processes in lower organisms since the simplicity of these systems may lead to a better understanding of the phylogenetic development of xenobiotic metabolism. 

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