Detoxification of Xenobiotics Flashcards
What is a xenobiotic?
A compound that is foreign to the body
xenos = stranger
Where does detoxification of xenobiotics take place?
The liver
What are the principal classes of xenobiotics that are medically relevant?
pharmaceuticals, chemical carcinogens, petroleum products, and some pesticides
How are xenobiotics detoxified for removal?
Polar bonds are attached to the compound to increase water solubility of the xenobiotic, facilitating excretion from the body.
What is phase 1 metabolism of xenobiotics?
It involves isoforms of cytochrome P450s
What is the chief reaction involved in phase 1 metabolism?
Hydroxylation
What group of hemoproteins do cytochrome P450 come from?
Mono-oxygenases
What are the co-factors of phase 1?
Niacin, Riboflavin, and Iron
Where are CYP enzymes found?
In the ER and mitochondria.
What tissues are most CYP enzymes found?
Liver (MOSTLY), adrenals, kidney
Interfacing between internal and external environments: lungs and intestine
What is an enzymatic variation of CYP?
Some cytochrome p450s exist as polymorphs. Variation in enzyme activity can be found from person to person.
What are phase 2 reactions?
They are conjugation reactions that make the xenobiotic more water soluble for excretion via the urine or bile.
What are the 6 principal types of phase 2 reactions?
Glutathionation, glucuronidation, addition of amino acids, acetylation, sulfation, and methylation.
What is glutathionation?
Addition of glutathione to a xenobiotic
What is glucuronidation?
Addition of a sugar (UDP-glucuronate) to a xenobiotic
What is addition of an amino acid for detoxification?
A xenobiotic added to an amino acid (glycine or taurine)
What is acetylation of a xenobiotic?
Acetyl CoA gives its acetyl group to the xenobiotic
What is sulfation of a xenobiotic?
PAPS is combine with a xenobiotic to place the sulfur on the xenobiotic and frees the PAP.
What is methylation of a xenobiotic?
Methyl groups are donated to the xenobiotic
What are responses to xenobiotics?
Pharmacologic, toxic, immunologic, or carcinogenic.
What are negative pathways of xenobiotic detoxification?
Covalent binding to macromolecules that lead to: Mutation (cancer), Hapten (antibody production leading to cell injury), and Cell Injury
