Lipophilic toxicants, metabolic transformation

Metabolic transformation of lipophilic toxicants including pesticide and plant allelochemicals to excretable products usually proceeds by a series of enzymatic events to ultimately detoxify the chemical. Many of the initial reactions can generate intermediates... 

Humans are exposed continuously and unavoidably to a myriad of potentially toxic chemicals that are inherently lipophilic and, consequently, very difficult to excrete. To effect their elimination, the human body has developed appropriate enzyme systems that can transform metabolically these chemicals to hydrophilic, readily excretable, metabolites. This biotransformation process occurs in two distinct phases. Phase I and Phase II, and involves several enzyme systems, the most important being the cytochromes P450. The expression of these enzyme systems is regulated genetically but can be modulated also other factors, such as exposure to chemicals that can either increase or impair activity. Paradoxically, the same xenobiotic-metabolizing enzyme systems also can convert biologically inactive chemicals to highly reactive intermediates that interact with vital cellular macromolecules and elicit various forms of toxicity. Thus, xenobiotic metabolism does not always lead to deactivation but can result also in metabolic activation with deleterious consequences. 

A great deal can occur to a xenobiotic between its introduction to the environment and its interaction at the site of action. Many materials are altered in specific ways depending upon the particular chemical characteristics of the environment. Bioaccumulation, the increase in concentration of a chemical in tissue compared to the environment, often occurs with materials that are more soluble in lipids and organics (lipophilic) than in water (hydrophilic). Compounds are often transformed into other materials by the various metabolic systems that reduce or alter the toxicity of materials introduced to the body. This process is biotransformation. Biodegradation is the... 

Fiirst Sandor utca 5 H-1136 Budapest, Hungary Tel. 36-1-112-4874, fax 36-1-132-2574 Prediction of metabolic products based on a library of known transformations. HARZARDEXPERT for prediction of toxicity. MOLIDEA for molecular modeling, molecular mechanics CNDO/2 and CNDO/S calculations. DRUGIDEA for QSAR. LABSWARE for general computations and statistics. PRO-LOGP for lipophilicity calculation using R. F. Rekker method. PC. 

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