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 have lead to the proposal of
modulating metabolizing enzymes as a useful approach for human
health benefits. Importantly, many of these chemical compounds are
present in human daily diets. There are many advances that have
been made in the past decades towards the understanding of
functions and implications of activation enzymes and detoxification
enzymes. An organized, concise overview is needed for the readers
who are initially exposed to this important subject, particularly
for students and researchers in the areas of biomedical sciences,
biochemistry, nutrition, pharmacology and chemistry. This book is
intended to serve this purpose as an introduction to the subject.
Furthermore, major topics in the book, excluding catalytic
reactions and structural properties, may have interest to other
readers who have knowledge of basic sciences and understanding
enzyme related information. The book discusses subjects associated
with foreign compound metabolizing enzymes with emphasis on
biochemical aspects, including lipophilic foreign compounds,
catalytic properties, reactive intermediates, biomedical and
biochemical effects, genetic polymorphisms, enzyme inducibility,
enzyme modulation for health benefits, dietary related enzyme
modulators, and structural characteristics of enzyme inducers.
General
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