Biotransformations xenobiotic

Herbivores biotransforms xenobiotics from natural or artificial sources to render them harmless. Disarming potentially toxic compounds is termed detoxication, while the term detoxification refers to correcting a state of toxicosis (Johns, 1990). Herbivores degrade secondary plant compounds in a variety of ways, starting in the mouth, and leading to excretion. 

Plants have been shown to biotransform xenobiotic organic compounds (Komossa and Sandermann, 1995 Pflugmacher and Sandermann, 1998). Historically, much of the information on plant biotransformation of organic compounds has been obtained from studies examining intentionally applied chemicals such as herbicides and pesticides. More recently, the biotransformation of nonherbicide organics has been investigated... 

The metabolism of foreign compounds (xenobiotics) often takes place in two consecutive reactions, classically referred to as phases one and two. Phase I is a functionalization of the lipophilic compound that can be used to attach a conjugate in Phase II. The conjugated product is usually sufficiently water-soluble to be excretable into the urine. The most important biotransformations of Phase I are aromatic and aliphatic hydroxylations catalyzed by cytochromes P450. Other Phase I enzymes are for example epoxide hydrolases or carboxylesterases. Typical Phase II enzymes are UDP-glucuronosyltrans-ferases, sulfotransferases, N-acetyltransferases and methyltransferases e.g. thiopurin S-methyltransferase. 

The numerous biotransformations catalyzed by cytochrome P450 enzymes include aromatic and aliphatic hydroxylations, epoxidations of olefinic and aromatic structures, oxidations and oxidative dealkylations of heteroatoms and as well as some reductive reactions. Cytochromes P450 of higher animals may be classified into two broad categories depending on whether their substrates are primarily endogenous or xenobiotic substances. Thus, CYP enzymes of families 1-3 catalyze... 

Metabolic pathways containing dioxygenases in wild-type strains are usually related to detoxification processes upon conversion of aromatic xenobiotics to phenols and catechols, which are more readily excreted. Within such pathways, the intermediate chiral cis-diol is rearomatized by a dihydrodiol-dehydrogenase. While this mild route to catechols is also exploited synthetically [221], the chirality is lost. In the context of asymmetric synthesis, such further biotransformations have to be prevented, which was initially realized by using mutant strains deficient in enzymes responsible for the rearomatization. Today, several dioxygenases with complementary substrate profiles are available, as outlined in Table 9.6. Considering the delicate architecture of these enzyme complexes, recombinant whole-cell-mediated biotransformations are the only option for such conversions. E. coli is preferably used as host and fermentation protocols have been optimized [222,223]. 

Radulovic LL, Kulkami AP, Dauterman WC. 1987. Biotransformation of methyl parathion by human foetal liver glutathione S-transferases An in vitro study. Xenobiotic 17 105-114. 

In phase 1, the pollutant is converted into a more water-soluble metabolites, by oxidation, hydrolysis, hydration, or reduction. Usually, phase 1 metabolism introduces one or more hydroxyl groups. In phase 2, a water-soluble endogenous species (usually an anion) is attached to the metabolite— very commonly through a hydroxyl group introduced during phase 1. Although this scheme describes the course of most biotransformations of lipophilic xenobiotics, there can be departures from it. 

The enzymes involved in the biotransformation of pollutants and other xenobiotics will now be described in more detail, starting with phase 1 enzymes and then moving on to phase 2 enzymes. 

Examples of the Range of Plasmids Carrying Genes Coding Enzymes for the Biodegradation or Biotransformation of Xenobiotics... 

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. 

A second area of drug discovery and development in which enzyme reactions play a critical role is in the study of drug metabolism and pharmacokinetics. The elimination of xenobiotics, including drug molecules, from systemic circulation is driven by metabolic transformations that are entirely catalyzed by enzymes. Table 1.2 lists some of the enzyme-catalyzed transformations of xenobiotics that commonly contribute to drug molecule elimination. These biotransformation reactions... 

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