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21 Cards in this Set
- Front
- Back
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Why is Dioxin so toxic? (about 4 reasons covered)
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1. It up regulates CYP1A1 but it barely recognizes it.
2. Dioxin competes for Ah receptor that is necessary for immune and liver function 3. Very slowly metabolized 4. Activates other CYPs to make toxic products |
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What are the three metabolic paths that acetaminophen can take - (in order)
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1. Glucuronidation
2. Sulfation 3. Glutathionation |
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What is the metabolic intermediate of acetaminophen that is highly toxic to the liver?
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NAPQI (N-acetyl-p-benzoquinoneimine)
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Why does metabolism of acetaminophen skip phase I?
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Bc it already has a polar hydroxyl group attached to it.
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Why is acetaminophen toxicity more likely in the fasted state?
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Bc the UDPGA required for glucuronidation of APAP is preoccupied in gluconeogensis. This pushes the APAP metabolism down sulfation (safe) and down CYP2E1 pathway to NAPQI (toxic)
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Why is acetaminophen toxicity more likely in the alcoholics?
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EtOH increases CYP2E1 - this will metabolize more APAP to NAPQI.
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Why is N-acetylcystein (NAC) used as an antidote to APAP toxicity?
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Bc NAC is a precursor to Glutathione - the constituent that is added to NAPQI to turn it into a nontoxic metabolite. Normally, there is not enough GSH to deal with the NAPQI load...NAC helps.
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If you're on a statin, what fruit would you not want to take? Why? (p421)
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Grapefruit juice. Bc it is rich in naringenin and quercitin which inhibit CYP3A4 - necessary for metabolism of CVD drugs - and leave high concentrations of the drugs in the blood
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What might an iron deficiency cause? Why?
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A decrease in activity of P450s and increased levels of drugs in the circulations. This is bc heme is a required component of P450s
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What is riboflavin converted to? How does its availability influence P450 activity?
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FMN and then FAD. It is an important prosthetic group of cytochrome P450 reductase.
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What CYP discussed in class has ethnic differences resulting in different metabolic rates? Without it Asians cannot catalyze the oxidation of:
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CYP2D6. Debrisoquine
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What is the leading cause of mental retardation in the US? How many individuals does it affect/yr?
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FAS. 1-2 births per 1000
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Alcohol dehydrogenase converts ethanol to:
And uses what in the process? Where does this take place? |
Acetaldehyde. Requires NAD+. Cytosol
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Why is acetaldehyde toxic?
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Bc if forms covalent bonds with proteins, impairing their function - can damage liver, leading to death.
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Liver damage from excessive EtOH consumption occurs in three stages:
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1. Fatty liver
2. Alcoholic hepatitis: inflammation and groups of cells die 3. Cirrhosis: scar tissue impairs the liver's biochemical functions. |
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What enzyme catalyzes the second step in EtOH metabolism? What is used in the process? Where does it take place?
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Aldehyde Dehydrogenase.
Requires NAD+. Mitochondria |
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Excessive alcohol consumption results in an excess of what?
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NADH
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High concentrations of NADH will offset the balance of NAD+ necessary for other pathways. Two symptoms commonly resulting from this include:
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Fasting hypoglycemia and fatty liver
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High concentrations of NADH inhibits gluconeogenesis by preventing:
As a result, the reverse reaction will predominate and this will accumulate resulting in ?? and ?? |
The oxidation of lactate to pyruvate. The reverse rxn will cause lactate to accumulate with hypoglycemia and lactic acidosis symptoms.
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Why does acetylCoA accumulate in alcoholics?
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Bc NADH accumulates and inhibits TCA enzymes alpha-ketoglutarate dehydrogenase and isocitrate dehydrogenase. Thus acetylCoA cannot enter the TCA cycle and it results in 1) ketone bodies released into blood and enhancing the acidic condition that already exists from the high lactate concentration and 2) processing of acetate in the liver becomes more inefficient, leading to a buildup of the reactive molecule acetaldehyde.
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What vitamin is affected by ethanol? what are the consequences of this?
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Vitamin A (retinol) is converted into retinoic acid with the same dehydrogenases that metabolize ethanol. Thus EtOH acts as a competitive inhibitor preventing conversion of vitamin A to retinoic acid. FAS (at least partially) and cancer.
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