Polymorphisms and toxic metabolites Flashcards
Which of the CYPS is most represented?
CYP2
What three categories define metabolic activity?
- Extensive metaboliser
- Poor metaboliser
- Ultra rapid metaboliser
Grape fruit juice is a potent CYP3A4 inhibitor. TRUE OR FALSE?
TRUE
Which one of the CYPs is unique?
CYP2E1
What do CYP2E1 produce?
Reactive oxygen radicals through reduction of oxygen
Ethanol strongly induces the production of reactive oxygen radicals via reduction of oxygen. TRUE OR FALSE?
TRUE
Where is CYP2E1 located?
Located in the ER
CYP2E1 primarily located in the rows of 5 cells around the central venules of a liver lobule. TRUE OR FALSE?
TRUE
Name two substrate that can inhibit and induce?
Ethanol and Acetone
Name two substrate that inhibit but does not induce?
Paracetamol and carbon tetrachloride
Name an inducer that is not a substrate?
Imidazole
CYP2E1 is increased in diabetes, obesity and other nutritional states that produce acetone. TRUE OR FALSE?
TRUE
Action of alcohol dehydrogenase and aldehyde dehydrogenase leads to accumulation of NADH. TRUE or FALSE?
TRUE
CYP pathway generates free radicals, consumes NADPH and depletes glutathione levels. TRUE OR FALSE?
TRUE
NADH does not lead to release of ketone bodies and high levels of actetaldehyde, resulting in liver damage and death. TRUE OR FALSE?
FALSE
What toxic metabolite is produced when paracetamol is metabolised?
NAPQI
During Glutathione conjugation the conjugates are less toxic than the parent compound. TRUE OR FALSE?
TRUE
The conjugates of glutathione conjugation are excreted in bile or via the kidney. TRUE OR FALSE?
TRUE
How is paracetamol toxicity metabolised?
-Sulfation or glucuronidation
NAQPI is an electrophile and will react with nucleophilic centres. TRUE OR FALSE?
TRUE
Glutathione a sacrificial nucleophile protects cellular SH groups. TRUE OR FALSE?
TRUE
Ethanol is not a CYP2E1 substrate so does not compete with other substrates before CYP2E1 is induced. TRUE OR FALSE?
TRUE
CYP2E1 metabolism of paracetamol is reduced when drug is administered alongside ethanol. TRUE OR FALSE?
TRUE
Name an antidote for paracetamol toxicity?
Methionine
