Study Set Content:
The (blank) of the inducer-receptor complex into the
nucleus, followed by ligand-induced dimerization with
(blank), a closely related nuclear protein, leads to
subsequent activation of regulatory elements of CYP1A
genes, resulting in their induction.
,translocation, Arnt
This is also the mechanism of CYP1A induction by
cruciferous vegetables, and the proton pump inhibitor,
omeprazole
- a member of the steroid-retinoid-
thyroid hormone receptor family, has recently been shown to
mediate CYP3A induction by various chemicals (dexamethasone,
rifampin, mifepristone, phenobarbital, atorvastatin, and hyperforin
- a constituent of St. John’s wort) in the liver and intestinal mucosa.
Pregnane X receptor (PXR)
a constituent of St. John’s wort)
hyperforin
has been identified
for the relatively large and structurally diverse phenobarbital class
of inducers of CYP2B6, CYP2C9, and CYP3A4
Constitutive Androstane Receptor (CAR)-
highly
expressed in liver and kidneys, which uses lipid lowering drugs (eg,
fenofibrate and gemfibrozil) as ligands. Consistent with its major
role in the regulation of fatty acid metabolism,
Peroxisome Proliferator Receptor ɑ (PPAR-ɑ)
mediates
the induction of CYP4A enzymes, responsible for the metabolism of
fatty acids such as arachidonic acid and its physiologically relevant
derivatives.
PPAR-ɑ
Imidazole-containing drugs such as (blank) bind tightly to the P450 heme iron and
effectively reduce the metabolism of endogenous
substrates (eg, testosterone) or other co-administered
drugs through competitive inhibition.
cimetidine and
ketoconazole
(blank) derivatives are
metabolized, apparently by CYP3A, to metabolites that
complex the cytochrome P450 heme iron and render it
catalytically inactive.
troleandomycin,erythromycin, and erythromycin
which binds tightly to the heme iron and quasi-irreversibly
inactivates the enzyme, thereby inhibiting the metabolism
of potential substrates.
Inhibitor Proadifen
Inhibitor Proadifen used in research),
(SKF-525-A,
inactivators that attack the heme or
the protein moiety—includes:
Suicide inhibitors
Suicide inhibitors includes
certain steroids (ethinyl estradiol,
norethindrone, and spironolactone);
fluroxene;
• Allobarbital
• the analgesic sedatives
allylisopropylacetylurea, diethylpentenamide,
and ethchlorvynol;
• carbon disulfide;
• grapefruit furanocoumarins;
• selegiline;
• phencyclidine;
• ticlopidine and clopidogrel;
• ritonavir; and propylthiouracil.
• secobarbital is found to inactivate CYP2B1
by modification of both its heme and protein
moieties
Commonly called conjugation reaction, because they have a
functional group of the xenobiotic to add or conjugate a biomolecule
that usually increase the polarity of the xenobiotic and facilitates the
elimination from the body.
PHASE II REACTION
Parent drugs or their phase I metabolites that contain suitable
chemical groups often undergo coupling or conjugation reactions
with an endogenous substance to yield
drug conjugates
In general, conjugates are (blank)molecules that are
readily excreted and often inactive.
polar
Conjugate formation involves high-energy intermediates
and specific
Transfer enzymes
Transfer a high energy molecule called co-factor or
co- substrate to the xenobiotic
Transferase-
Transferase An enzyme located in
microsomes or in the cytosol
are the most dominant enzymes
uridine 5′-diphosphate (UDP)-glucuronosyl
transferases ( UGTs)
