4 Liver Biochemistry Flashcards
What allows greater access and increased contact between liver and blood
- lack of tight junctions and basement membrane
- gaps between endothelial cells
- fenestrations in endothelial cells
- low portal BP
Isoprenoids are made of
3 ACoA
What do isoprenoids make
Steroids, lipid-soluble vitamins, and prenyl groups
Where is ACoA generated
Mitochondria
What is ACoA
Decarboxylated pyruvate
How is ACoA transported
Citrate shuttle
Six units of IPP form
Sterane ring (backbone of most steroids)
What is the rate limiting step of cholesterol synthesis
HMG CoA reductase
What increases HMG CoA reductase activity
Insulin and thyroxine
What decreases HMG CoA reductase activity
Glucagon, sterols, high AMP, Vit E, statins
What inhibits the conversion of lanosterol —> cholesterol
Azoles, KCN, tamoxifen, morpholine, triparanol, AY-9944
Statins lead to
Increased transcription of LDL receptor
What converts cholesterol into bile acids
7-α hydroxylase
Antimycotics inhibit what cholesterol steps
Lanosterol to cholesterol
Ketoconazole inhibits conversion of
Cholesterol to bile acids through 7α hydroxylase
Antiestrogens prevent conversion
Demosterol to cholesterol
What do antiepileptic drugs do to cholesterol
Inhibits conversion of squalene to lanosterol and cholesterol trafficking
Cholic acid forms what
Cholyl CoA pKa 6
Cholyl CoA + taurine makes
Taurocholic acid pKa 2
Cholyl CoA + glycine =
Glycoholic acid pKa 4
Gallstones lead to what chronic issues
Malabsorption syndromes and deficiencies in fat soluble vitamins
Which CYP are responsible for drug metab
1,2, 3
Inhibiting CYPs causes an increase in statins which can lead to
Myopathy and rhabdomyolysis
What are some inhibitors in CYP
Itraconozole, clarithromycin, and cyclosporine, citrus
What are some CYP inducers
Rifampicin, carbamazepine, St John’s wort
What does the liver store in excess
Glucose, vitamin A, vitamin D, iron
What is the toxic byproduct of chloramphenicol
Aniline
IPP can be converted to
tRNA
Farnesyl PP is conververed to
Dolichol - protein glycosylation
Ubiquinone
Heme A
RAS
What processes are interrupted by statins
tRNA synth
Protein glycosylation
CoQ, electron transport
RAS
What inhibits squalene synthase
Lapaquistat
What is the toxic intermediate produced by acetaminophen
NAPQI
What is the rate limiting step of bile salt synthesis
Cholesterol to 7α hydroxycholesterol by 7α hydroxylase
What inhibits 7a hydroxylase? Stimulates
Bile acids; cholesterol
What inhibits recycling of bile salts
Cholestyramine
What causes statin myopathy
Depletion of ubiquinone (CoQ10) and resultant impairment of mitochondrial function
Inhibitors of squalene synthase should ______ levels of CoQ10 in muscles
Increase
