Overview.- Lipophilic Foreign Compounds.- Metabolic Conversion of Lipophilic Compounds.- Phase I Enzymes.- Phase II Enzymes.- Reactive Intermediate Formation.- Biomedical and Biochemical Effects.- Genetic Variations in Metabolizing Enzymes.- Inducibility of Metabolizing Enzymes.- Induction and Inhibition Compounds.- Diets Rich in Enzyme Modulators.- Induction of Enzymes for Health Benefits.- Sources of Foreign Compounds.- Catalytic Reactions of Phase I Enzymes.- Catalytic Reactions of Phase II Enzymes.- Diversified Classes of Enzyme Modulators.- Conclusion.- Index.
Humans are exposed to foreign compounds such as drugs, household products and environmental chemicals by swallowing or breathing. Also, food is considered a foreign compound. Such foreign compounds can be non-essential and non-functional to life, and commonly are referred to as xenobiotics. Some xenobiotics are not toxic; however, many of them are potentially toxic or become toxic after conversion to metabolic intermediates. A considerable number of foreign compounds belong to non-polar, lipophilic substances. Lipophilic compounds are not soluble in water. Metabolic conversion of lipophilic foreign compounds to facilitate their removal from the body is essentially carried out by biochemical reactions catalyzed by two classes of metabolizing enzymes, namely, activation enzymes and detoxification enzymes.
Activation enzyme-catalyzed functionalization reaction introduces a functional group to a lipophilic compound. Functionalization modifies many foreign compounds to form reactive intermediates capable of interacting with cellular components (proteins, DNA and lipids), leading to a variety of conditions for diseases. Functionalized compounds are further metabolized through detoxification enzyme-catalyzed reactions, which result in an increase in the solubility of parent compounds and an inactivation of metabolic intermediates, thus facilitating their excretion from the body. To minimize the exposure of potentially toxic metabolic intermediates, it is essential to keep them at a minimum level.
Extensive investigations have revealed that foreign compound-metabolizing enzymes exhibit genetic polymorphisms. Variations in their activities can produce different results as to the susceptibility to potential toxic effects. Moreover, the expressions of activation enzymes and detoxification enzymes are inducible. A number of chemical compounds are capable of acting as modulators for these two classes of enzymes. These findings
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