Study Set Content:
alone is responsible for the metabolism of over
50% of the prescription drugs metabolized by the liver
CYP3A4
Many drug metabolizing enzymes are located in the
lipophilic
endoplasmic reticulum membranes of the liver and other tissues.
lipophilic
endoplasmic reticulum membranes of the liver and other tissues.
- Microsomes
- Mixed function oxidases (MFOs)
- Monooxygenase
The activity of these enzymes requires both a reducing agent
(nicotinamide adenine dinucleotide phosphate (NADPH)
and molecular oxygen.
In a typical reaction, one molecule of
(blank) is consumed (reduced) per substrate molecule, with one
oxygen atom appearing in the product and the other in the form of
oxygen,water
Co-factor is an essential electron donor in all organisms
NADPH
NADPH Used in anabolic processes:
calvin cycle, lipid nucleic
acid synthesis as a reducing agent.
In this oxidation-reduction process, two microsomal enzymes play a
key role:
NADPH cytochrome P450
oxidoreductase (POR and CPR)
cytochrome 450
A flavoprotein, One mole of this enzyme contains 1 mol each of flavin
mononucleotide (FMN) and flavin adenine dinucleotide
(FAD)
NADPH cytochrome P450
oxidoreductase (POR and CPR)
A hemoprotein called (blank)
- Serves as the terminal oxidase. In fact, the microsomal
membrane harbors multiple forms of this hemoprotein,
and this multiplicity is increased by repeated
administration of or exposure to exogenous chemicals.
cytochrome 450
Induction of cytochrome P450 System may increase
biotransformation.
If two drugs or compounds are competing for the
active site of the same enzyme, then one of the drugs will have a
decreased rate of transformation
Inhibition
Some of the chemically dissimilar P450 substrate
drugs, on repeated administration, induce P450 expression by
enhancing the rate of its synthesis or reducing its rate of
degradation
results in accelerated substrate metabolism and
usually in a decrease in the pharmacologic action of the inducer
and also of coadministered drugs.
Induction
However, in the case of drugs metabolically transformed to
reactive metabolites, enzyme induction may (blank)
metabolite-mediated toxicity
exacerbate
are also capable of inducing P450 enzymes.
Environmental chemicals Pollutants
As previously noted, exposure to (balnk)[ a ]pyrene and
other (blank), which are present
in tobacco smoke, charcoal-broiled meat, and other
organic pyrolysis products, is known to induce CYP1A
enzymes and to alter the rates of drug metabolism.
benzo, polycyclic aromatic hydrocarbons
which were once
used widely in industry as insulating materials and
plasticizers,
polychlorinated biphenyls (PCBs),
a trace by product of the chemical synthesis of
the defoliant 2,4,5-T
2,3,7,8- tetrachlorodibenzo- p -dioxin (dioxin,
TCDD),
A cytoplasmic receptor for polycyclic aromatic hydrocarbons
(eg, benzo[ a ]pyrene, dioxin)
AhR
