Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
37 Cards in this Set
- Front
- Back
|
principle route for metabolism of ethanol
|
hepatic alcohol dehydrogenases
|
|
|
what do hepatic alcohol dehydrogenases do to ethanol
|
oxidize it to acetaldehyde in cytosol
|
|
|
where is acetylaldehyde further oxidized by acetylaldehyde dehydrogenase to acetate
|
principally in the mitochondria
|
|
|
where is 10-20% of ingested ethanol oxidized
|
microsomal ethanol oxidizing system (MEOS)
|
|
|
what does MEOS consist of
|
cytochrome P450 in ER (CYP2E1)
|
|
|
when is ethanol oxidation have a higher proportion oxidied via MEOS
|
high ethanol concentrations and chronic consumption
|
|
|
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"
|
|
|
alcohol-induced liver disease
|
"alcohol-induced hepatitis, hepatic steatosis (fatty liver), cirrhosis"
|
|
|
principle toxic products of ethanol metabolism
|
acetaldehyde and free radicals
|
|
|
anion gap
|
subtract sum serum Cl- and serum HCO3- from serum Na+ concentration
|
|
|
what does a anion gap greater than normal indicate
|
suggests that acids like ketone bodies are present in the blood in increased amounts
|
|
|
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"
|
|
|
what percent of ethanol is converted to acetate in the liver
|
~90%
|
|
|
electron donor and acceptor in MEOS
|
NADPH is additional electron donor and O2 is electron acceptor
|
|
|
most common ADH in ethanol metabolism
|
ADH1 - liver alcohol dehydrogenase
|
|
|
where do ADH4 enzymes contribute to risk of cancer with heavy drinking
|
upper GI tract
|
|
|
what ALDH converts most acetaldehyde to acetate
|
ALDH2 which has a high affinity and is highly specific
|
|
|
accumulation of what causes nausea and vomiting in ethanol metabolism
|
acetaldehyde
|
|
|
disulfiram
|
ALDH inhibitor used frequently to treat alcoholism
|
|
|
"what does the ""2E1"" represent in CYP2E1"
|
"2-family, E-subfamily, 1-number of individual enxymes within subfamily"
|
|
|
increase in CYP2E1 with ethanol consumption occurs via what mechanisms
|
"transcriptional, posttransciptional, and posttranscriptional regulation"
|
|
|
phenobarbitol and ethanol consumption
|
inactivates metabolism of phenobarbitol causing potential toxic elevation of the drug
|
|
|
wernicke-Korsakoff syndrome
|
neuropsychiatric syndrome commonly associated with alcoholism
|
|
|
what makes women lightweights
|
"higher fast content, generally smaller size, less ADH activity"
|
|
|
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
|
|
|
why does adipose tissue lipolysis increase after ethanol consumption
|
possible because of epinephrine release
|
|
|
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
|
|
|
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"
|
|
|
what occurs to lactate dehydrogenase rxn with high NADH/NAD+ ratio
|
"shifted toward lactate, resulting in lacticacidosis"
|
|
|
why are patients with gout advised against drinking ethanol
|
elevated blood lactate may decrease excretion of uric acid by kidney
|
|
|
what other consequence occurs with lactate formation
|
aas that generally enter gluconeogenesis are converted to lactate from pyruvate and can't enter gluconeogenesis
|
|
|
how can ethanol with a meal result in transient hyperglycemia
|
NADH/NAD+ ratio inhibits glycolysis at the glyceradehyde 3-phosphate dehydrogenase step
|
|
|
what does acetaldehyde accumulate through in ethanol metabolism
|
alcohol dehydrogenases and MEOS
|
|
|
what does acetaldehyde do once released into blood
|
"highly reactive and binds covalently to amino groups, sulfhydryl groups, nucleotides, and phospholipids to form 'adducts'"
|
|
|
proteins affected by 'adducts'
|
"synthesis of calmodulin, ribonuclease, and tubulin, plus others in liver and some in other tissues"
|
|
|
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
|
|
|
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
|
