Xenobiotic metabolizing system

SOHN O S, SURACE A, FIALA E S, RICHIE J P, COLOSIMO S, ZANG E and WEISBURGER J H (1994) Effects of green and black tea on hepatic xenobiotic metabolizing systems in the male F344 mt , Xenobiotica, 24, 119-27. 

Nakata, K., Tanaka, Y., Nakano, T., Adachi, T., Tanaka, H., Kaminuma, T., and Ishikawa, T. (2006) Nuclear receptor-mediated transcriptional regulation in Phase I, II, and III xenobiotic metabolizing systems. Drug Metab. Pharmacokinet. 21, 437-457. 

Built-in non-discriminatory activity has, however, got a down side the immunological system sometimes sees self as foreign and becomes self destructive and the xenobiotic metabolic system sometimes generates products more reactive and biologically destructive than the original substrate. 

Like Derek for Windows, the Meteor xenobiotic metabolism system has also recently been reviewed. It shares many commonalities with Derek for Windows (and indeed was developed from a common computer-code base) in terms of, for example, the processing of query structures with different constraints, the viewing of results and the generation of reports using different filters. The Meteor knowledge base is composed of a biotransformation dictionary, rules and example metabolic reactions. The biotransformation dictionary consists of... 

Microbial Transformations and Interactions with the Xenobiotic Metabolizing Enzyme (XME) System... 

Figure 3 Some interactions between gastrointestinal bacteria and the xenobiotic metabolizing enzyme system of the host. Solid lines, host XME system reactions dotted lines, classes of reactions mediated by gastrointestinal bacteria. Specific examples of reaction classes 1-5 are cited in the text. (Modified from Rowland and Tanaka " )...

Talafous J, Sayre LM, Mieyal JJ, Klopman G. META. 2. A dictionary model of mammalian xenobiotic metabolism. J Chem Inf Comput Sci 1994 34 1326-33. Klopman G, Tu M, Talafous J. META. 3. A genetic algorithm for metabolic transform priorities optimization. J Chem Inf Comput Sci 1997 37 329-34. Langowski J, Long A. Computer systems for the prediction of xenobiotic metabolism. Adv Drug Del Rev 2002 54 407-15. 

Donnarumma L, G de Angelis, F Gramenzi, L Vittozzi (1988) Xenobiotic metabolizing enzyme systems in test fish. III. Comparative studies of liver cytosolic glutathione S-transferases. Ecotoxicol Environ Saf 16 180-186. 

Computer systems for the prediction of xenobiotic metabolism, Adv. Drug Deliv. Rev., 2002, 54, 407-415. 

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. 

A selection of carboxylic ester hydrolases (EC 3.1.1) of major or more-modest significance in xenobiotic metabolism is given in Table 2.5. The recommendations of the Enzyme Nomenclature Committee on the classification of esterases cannot be considered completely satisfactory, but, even after decades of debate, a more satisfactory classification system remains to be proposed [56] [57], The main difficulties with esterase classification have been summarized as follows [58],... 

A recent paper clearly highlighted the limitations of in vitro systems in modeling whole-organism responses, which should be considered when developing biomarkers of in vivo toxicity. Dere and colleagues (58) compared the temporal gene expression profiles of Hepalclc mouse hepatoma cells and of the mice liver after treatment with a dioxin. The analysis revealed that Hepalclc cells were able to model the induction of xenobiotic metabolism in vivo. On the other hand, responses associated with cell cycle progression and proliferation were unique to the in vitro system, while lipid metabolism and immune responses were not replicated effectively in the Hepalclc cells. 

The cytochrome P450 system is the principal enzyme system for the metabolism of lipophilic xenobiotics. It is a heme-containing, membrane-bound, multi-enzyme system which is present in many tissues in vivo but is present at the highest level in liver. A coenzyme, cytochrome P450 NADPH oxidoreductase (OR), is essential for P450 catalytic function and cytochrome bs may stimulate catalytic activities of some enzymes. In human liver, it is estimated that there are 15-20 different xenobiotic-metabolizing cytochrome P450 forms. A standard nomenclature, based on relatedness of the amino acid sequences, has been developed (Nelson et al., 1993). The most recent... 

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