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37 Cards in this Set
- Front
- Back
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principle route for metabolism of ethanol |
hepatic alcohol dehydrogenases |
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what do hepatic alcohol dehydrogenases do to ethanol |
oxidize it to acetaldehyde in cytosol |
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where is acetylaldehyde further oxidized by acetylaldehyde dehydrogenase to acetate |
principally in the mitochondria |
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where is 10-20% of ingested ethanol oxidized |
microsomal ethanol oxidizing system (MEOS) |
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what does MEOS consist of |
cytochrome P450 in ER (CYP2E1) |
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when is ethanol oxidation have a higher proportion oxidied via MEOS |
high ethanol concentrations and chronic consumption |
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acute effects of alcohol ingested |
"generation of NADH which increases NADH/NAD+ ratio of liver, which causes fatty acid oxidation to be inhibited and ketogenesis may occur" |
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alcohol-induced liver disease |
"alcohol-induced hepatitis, hepatic steatosis (fatty liver), cirrhosis" |
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principle toxic products of ethanol metabolism |
acetaldehyde and free radicals |
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anion gap |
subtract sum serum Cl- and serum HCO3- from serum Na+ concentration |
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what does a anion gap greater than normal indicate |
suggests that acids like ketone bodies are present in the blood in increased amounts |
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breakdown of ethanol metabolism |
"0-5% absorbed and metabolized in tongue, mouth, esophagus, and stomach; of remainder 85-98% enters blood and is metabolized by liver; 2-10% excreted through lungs or kidneys" |
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what percent of ethanol is converted to acetate in the liver |
~90% |
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electron donor and acceptor in MEOS |
NADPH is additional electron donor and O2 is electron acceptor |
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most common ADH in ethanol metabolism |
ADH1 - liver alcohol dehydrogenase |
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where do ADH4 enzymes contribute to risk of cancer with heavy drinking |
upper GI tract |
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what ALDH converts most acetaldehyde to acetate |
ALDH2 which has a high affinity and is highly specific |
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accumulation of what causes nausea and vomiting in ethanol metabolism |
acetaldehyde |
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disulfiram |
ALDH inhibitor used frequently to treat alcoholism |
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"what does the ""2E1"" represent in CYP2E1" |
"2-family, E-subfamily, 1-number of individual enxymes within subfamily" |
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increase in CYP2E1 with ethanol consumption occurs via what mechanisms |
"transcriptional, posttransciptional, and posttranscriptional regulation" |
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phenobarbitol and ethanol consumption |
inactivates metabolism of phenobarbitol causing potential toxic elevation of the drug |
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wernicke-Korsakoff syndrome |
neuropsychiatric syndrome commonly associated with alcoholism |
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what makes women lightweights |
"higher fast content, generally smaller size, less ADH activity" |
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what occurs to triacylglycerals formed due to high NADPH/NAD+ ratio |
incorporated into VLDLs with accumulate in liver and enter into blood causing ethanol-induced hyperlipidemia |
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why does adipose tissue lipolysis increase after ethanol consumption |
possible because of epinephrine release |
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what is the result of enough NADH production from ethanol oxidation and fatty acids that there is no need to oxidize acetyl CoA in the TCA cycle |
ketone body accumulation - acetoacetate and B-hydroxybutyrate |
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what causes additional accumulation of ketone bodies with ethanol consumption |
"acetate is the preferred fuel and is available, thus ketone bodies are not used quick enough" |
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what occurs to lactate dehydrogenase rxn with high NADH/NAD+ ratio |
"shifted toward lactate, resulting in lacticacidosis" |
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why are patients with gout advised against drinking ethanol |
elevated blood lactate may decrease excretion of uric acid by kidney |
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what other consequence occurs with lactate formation |
aas that generally enter gluconeogenesis are converted to lactate from pyruvate and can't enter gluconeogenesis |
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how can ethanol with a meal result in transient hyperglycemia |
NADH/NAD+ ratio inhibits glycolysis at the glyceradehyde 3-phosphate dehydrogenase step |
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what does acetaldehyde accumulate through in ethanol metabolism |
alcohol dehydrogenases and MEOS |
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what does acetaldehyde do once released into blood |
"highly reactive and binds covalently to amino groups, sulfhydryl groups, nucleotides, and phospholipids to form 'adducts'" |
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proteins affected by 'adducts' |
"synthesis of calmodulin, ribonuclease, and tubulin, plus others in liver and some in other tissues" |
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what is the consequence of acetaldehyde adducts of tubulin |
diminished secretion of serum proteins and VLDL from the liver; proteins accumulate in liver along with lipid |
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acetaldehyde and free radicals |
directly binds glutathione and diminishes its ability to protect against H2O2 and prevent lipid peroxidation; also binds free radical defense enzymes |
