Flashcards in Liver Detox & Alcohol Deck (84):
Cytochrome P450 oxidises all foreing chemicals with MW of?
Which Cytochrome P450 metabolises paracetomol?
Cytochrome P450 2E1
Where do you find Cytochrome P450 enzymes in the cell?
What is the formula for Cytochrome P450 monoxygenase catalyse?
RH + NADPH + H+ + O2 --> ROH + H2O + NADP+
What happens if CYP 2D6 is deficient?
failure to convert codeine to morphine
What does the initial alternation in Cytochrome P450 involve?
addition of -OH group and then a sugar to make it soluble
where is Cytochrome P450 located on the ER?
Cytochrome P450 is an enzyme? or a pigment?
P450 is in the microsomes? or the ER?
What colour are Microsomes?
What are the P450 in mitochondria used for?
oxidising steroids esp. in adrenals
Cytochromes (not P450) also function in what?
Food toxins do what to your P450?
promotes variants of P450, can train your liver to metabolize more toxins slowly
how many P450 genes in humans?
What is CYP, 2, A, 6?
Each family in P450 share ___% same sequence?
Each subfamily in P450 share ___% same sequence?
what does the hydrophobic protein foot of P450 enzymes do?
anchors P450 to a membrane eg. ER
are P450s inducible?
yes if substrates are persistently present
what makes P450 pink?
haem prosthetic group
What anchors the haem to the protein in P450?
P450 is a mono or di or tri-oxygenase?
how does P450 get collateral damage during oxidation?
reactive O2 species don't always hit their mark, since they are immediately next to substrate, it may damage P450 in process
peroxide usually attacks substate to form R-OH but when it doesn't, what does it create?
epoxides from P450 reaction gone awry does what?
highly reactive with DNA
imipramine is a tricyclic what? discovered how?
antidepressant, from a TB drug trial
What is the Ames test?
to see if your product has dioxins which are carcinogenic
aflatoxin from corn and nuts fungus contributes what severity of ?
kwashiorkor children have low what?
low albumin and high oedema
Drugs what induce P450 can do 3 things:
activate the gene dioxin/phenobarbital
protect P450 from turnover
dioxin induces CYP ____ leading to what?
cancer, birth defects, immunocompromise
how much dioxins needed to cause problems?
What was agent orange?
dioxins and benzopyrenes
Phenobarbital used for? acts where?
anesthetic by vets
acts on DNA
Some drugs where poor metabolisers have adverse reactions due to P450 polymorphisms include?
If CYP 2D6 is inactive what happens?
poor metabolism of codeine = no analgesic action
test for CYP 2D6 in patients how?
PCR with a kit
Is cirrhosis reversible?
how many Australians have health problems related to risky alcohol intake?
Aldehyde dehydrogenase converts acetaldehyde to acetate, what is acetate used for? 2 things
oxidised for energy or converted into fat
how fast to most people clear alcohol from their system?
1 standard drink per hour
should we completely abstain from alcohol?
no. moderate amounts confers better health and longevity
Fermenting to make alcohol was univeral to all civilisations except"
compare ethanol to fat
almost identical in energy content
how does alcohol depress nervous function?
ethanol disrupts membrane fats and make them more leaky and harder to fire properly
High risk to health, how many drinks for men and women?
Men = 6+
Women = 4+
small irreversibly shrunken brains affecting their entire lives
Alcoholic signs include? from head to toe
Heart disease and arrythmia
How fast does fatty liver develop? reversible or irreversible?
rapid development and reversible
3 presentations of alcohol induced liver damage?
alcoholic hepatitis with inflamm
50% of heavy drinkers present with fever and jaundice and abdo pain, what is the likely diagnosis?
alcoholic hepatitis with widespread inflamm
15-30% of heavy drinkers with extensive fibrosis and distorted internal liver structure are diagnosed with?
How much of your liver do you need to function normally?
How much alcohol entered system through stomach vs. gut?
how much of the alcohol is metabolized in liver? in lungs and kidneys? the rest?
<2% in lungs and kidneys
rest by stomach
what percentage of alcohol do you lose consciousness?
ethanol>acetylaldehyde>Acetate gets converted to what and then fed where?
acetyl CoA then into Krebs cycle
why do you feel faint if you have alcohol on an empty stomach?
Alcohol Dehydrogenase makes NADH which represses gluconeogenesis and leads to hypoglycemia = faintness
what is MEOS? how do it get activated?
microsomal ethanol oxidising system.
due to chronic alcohol: induces CYP2E1 four fold
Catalase is minor pathway
why are women affected by alcohol more?
alcohol does not distribute into fat as in men
three quick drinks raises you alcohol to?
How much alcohol in % can your liver clear per hour?
Why is alcohol clearance so slow?
alcohol dehydrogenase kinetics maxes out very fast
alcohol breath tests over or underestimates?
alcohol has 2 effects on drugs?
prevents drug clearance due to competition
promotes drug clearance due to elevated CYP 2E1
one really important drug alcohol affects
warfarin + alcohol =
a bad day.....
Hepatocytes are damaged via alcohol because 4 reasons
1 more free-radical damage due to decrease glutathione
2 dietary neglect
3. MEOS increases free radicals
4. increase iron catalyst for free radicals
Wernicke Korsakoff syndrome cause? and symptoms?
wide step, nystagmus, confusion, hypothermia, amnesia, confabulation
what is ALDH2?
acetylaldehyde dehydrogenase II in the mitochondrias and most important
acetylaldehyde dehydrogenase II inherited as recessive or dominant?
acetylaldehyde dehydrogenase II missing in ____% of Asians?
What is disulfiram/antabuse used for
inhibites aldehyde dehydrogenase = nausea, vomiting with alcohol consumption
Which could be a reward centre in the brain for alcohol?
Dopamine D2 receptor regulates reward reinforcement
What are Naltrexone, Nalmefene, Tiapride, Acamprosate used for?
neurological Rx to decrease craving and ease withdrawal with alcohol
Physical signs during examination for alcoholism?
spider naevi, palmar erythema, gynecomastia, change in body hair, peripheral neuropathy
Gamma-glutamyltranspeptidase (GGT) is what?
elevated in almost any liver disease, but could be increased in heavy drinkers even without liver damage or inflamm
is ALT elevated in alcohol liver damage?
what is carbohydrate deficient transferrin? when is it elevated?
marker for alcohol consumption greater than 4-5 drinks per day
why does alcohol cause dehydration
alcohol interferes with pituitary, less vasopression>less reabsorption of water>more peeing>dehydration
Alcohol causes most problems when in pregnancy?
in utero, first trimester
small irreversibly shrunken brains affecting their entire lives
definition of binge drinking?
more than 10 standard drinks in one sitting