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acetaminophen catabolized by CYP2E1 yields
NAPQI ( N acetyl-p-benzoquinoneimine)
what happends if large amount of acetaminophen is digested? how?
can be toxic. normally, NAPQI is toxic. However, certain amount of NAPQI is okay because it will be conjugated with glutathione by glutathione s transferase. But when there is overload of NAPQI due to overdose of acetaminophen, the body will run out of glutathione. Then NAPQI can damage cells.
enzyme that produces NAPQI from acetaminophen
this enzyme is induced by
induced by alcohol
explain acetaminophen metabolism in alcoholics
they have higher sensitivity to acetaminophen. they produce more CYP2E1 and build up more NAPQI
antidote for acetaminophen
what happends to majority of acetaminophen ingested
95% acetaminophen will be glucuronylated or sulfated. yielding acetaminphen glucuronate or acetaminophen sulfate.
5% digested by CYP2E1
T or F: CYP2E1 is a cytochrome P450
increase transcription of cytochrome P450 by activating xenobiotic receptors
this cytochrome p450 metabolizes 50% of all therpeutic drugs
what happens to drug when CYT P450 is iduced?
drug concentration decreases (more metabolized)
what food inhibits CYP3A4
predominant form of aflatoxin
aflatoxin B1 ( also most toxic aflatoxin)
two cytochromes that metabolizes aflatoxin B1
CYP1A2, CYP3A4, these activates aflatoxin B1 to 2,3 epoxide
DNA mutation caused by epoxide
G->T transversion. this inactivates p53 leading to hepatic carcinoma
T or F- most mutagens and carcinogens require activation
True ( has to be metabolized to active form)
drugs that increase the synthesis of CYT P450
phenobarbital, rifampin, carbamazepine
How many pseudogenes are there in CYP
flavoprotein reductase in the mitochondria
NADPH ferredoxin reductase
flavoprotein in the ER
NADPH cytochrome P450 reductase
accepts two electrons required for the monooxygenease reaction
NADPH dependent flavoprotein reductase
state of heme iron required for monooxygenation
ferrous state ( heme iron has to be reduced from ferric to ferrous)
terminal e- acceptor in the mammalian cells
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