Download METABOLISM OF XENOBIOTICS - Keluarga IKMA FKMUA 2010

METABOLISM OF
XENOBIOTICS
dr Agus Budiman
Xenobiotics ( Xenos = strange) are
compounds that are foreign to the body.
It includes drugs, food additives, pollutants
etc.
Understanding how xenobiotics are
handled at the cellular level is important in
learning how to cope with the chemical
attack.
Catabolism of xenobiotics
Metabolism of xenobiotics is considered
in:
phase 1: involved hydroxylation, catalyzed
by monooxygenases or cytochrome P450(
involved by NADPH).
phase 2: conjugation with glucuronic
acid,sulfate, acetate, glutathione, or
certain amino acids, or by methylation.
The overall purpose of the two phases is
to increase their water solubility( polarity)
and thus excretion from the body.
Xenobiotics are prodrugs or
procarcinogens.
Detoxification is usually used as terms to
metabolism of xenobiotics.
Cytochrome P450
Hemoprotein, like hemoglobin.
Widely distributed across species.
Present in highest amount in liver and small
intestines, mainly in the membranes of the
smooth endoplasmic reticulum.
Substrate specificity.
NADPH is involved in reaction mechanism in cyt
P450.
Lipids also components of cyt P450 system.
Most of cyt P450 are inducible.
Certain isoforms of cyt P450 involved in
metabolism of PAH( polycyclic aromatic
hydrocarbons) and called AHH( aromatic
hydrocarbon hydroxylases).
Certain cyt P450 exist in polymorphic
forms.
Conjugation reactions
Glucuronidation
Sulfation
Conjugation with glutathione
Acetylation e.g. in INH( isohydrazid)
Methylation
Activities of xenobiotics metabolism
affected by species, genetic factors,
gender, age.
Intake phenobarbital or certain
hydrocarbons can cause enzyme
induction.
The goal of xenobiotics metabolism is
make xenobiotics less poisonous or
nontoxic metabolite.