Study Set Content:
Xenobiotic biotransformation or drug metabolism is the process of converting lipophilic chemicals into()chemicals that are readily excreted.
hydrophilic
Various enzyme systems catalyze biotransformation.
o Hydrolysis o Reduction o Oxidation o Conjugation
. Generally, individual xenobiotic-biotransforming enzymes are located in a
single organelle
Generally, biotransformation is accomplished by a limited number of enzymes with () substrate specificities.
broad
expose or introduce a functional group that can be converted into a hydrophilic conjugate.
Hydrolysis, reduction, and oxidation
generally cause a modest increase in a xenobiotics water solubility while ()()()()cause a marked increase in hydrophilicity.
Oxidation, reduction, hydrolysis, methylation, and acetylation glucuronidation, sulfonation, glutathionylation, and amino acid conjugation
Xenobiotics can undergo biotransformation both by intermediary (endobiotic) enzymes and by enzymes within
gut microflora.
Certain endobiotics are biotransformed by ()
"xenobioticmetabolizing" enzymes.
Several xenobiotic-biotransforming enzymes are inducible. Xenobiotics can act as () for certain receptors (xenosensors).
ligands
can alter the biological properties of a xenobiotic.
Xenobiotic transformation
The toxicity and potential carcinogenicity of electrophilic metabolites produced by CYP and other xenobiotic biotransforming enzymes is reduced and often altogether eliminated by their conjugation with reduces
glutathione
Biotransformation of some xenobiotics results in the production of
ROS.
The balance between activation and detoxication by xenobiotic-biotransforming enzymes is often a key determinant of chemical toxicity, and is often the basis for organ or species differences in
toxicity
Enzymes are widely distributed in the body, the most concentrated being the
small intestine and liver
elimination
First-pass
differences
species
ot used in humans more in rats for toxicity studies.
Gender differences
study of causes, prevalence, and impact of heritable differences in xenobioticbiotransforming enzymes.
Pharmacogenetics –
– play an important role in the interaction between a xenobiotic and its biotransforming enzyme (from both a substrate and an inhibitor perspective), and xenobiotic-biotransforming enzymes can play a key role in converting one stereoisomer to another, a process known as mutarotation or inversion of configuration
Stereochemical aspects
– widely used to characterize the structure of metabolites.
Mass spectrometry
