4 Liver Biochemistry

Question 1

What allows greater access and increased contact between liver and blood

Answer 1

• lack of tight junctions and basement membrane
• gaps between endothelial cells
• fenestrations in endothelial cells
• low portal BP

Question 2

Isoprenoids are made of

Answer 2

3 ACoA

Question 3

What do isoprenoids make

Answer 3

Steroids, lipid-soluble vitamins, and prenyl groups

Question 4

Where is ACoA generated

Answer 4

Mitochondria

Question 5

What is ACoA

Answer 5

Decarboxylated pyruvate

Question 6

How is ACoA transported

Answer 6

Citrate shuttle

Question 7

Six units of IPP form

Answer 7

Sterane ring (backbone of most steroids)

Question 8

What is the rate limiting step of cholesterol synthesis

Answer 8

HMG CoA reductase

Question 9

What increases HMG CoA reductase activity

Answer 9

Insulin and thyroxine

Question 10

What decreases HMG CoA reductase activity

Answer 10

Glucagon, sterols, high AMP, Vit E, statins

Question 11

What inhibits the conversion of lanosterol —> cholesterol

Answer 11

Azoles, KCN, tamoxifen, morpholine, triparanol, AY-9944

Question 12

Statins lead to

Answer 12

Increased transcription of LDL receptor

Question 13

What converts cholesterol into bile acids

Answer 13

7-α hydroxylase

Question 14

Antimycotics inhibit what cholesterol steps

Answer 14

Lanosterol to cholesterol

Question 15

Ketoconazole inhibits conversion of

Answer 15

Cholesterol to bile acids through 7α hydroxylase

Question 16

Antiestrogens prevent conversion

Answer 16

Demosterol to cholesterol

Question 17

What do antiepileptic drugs do to cholesterol

Answer 17

Inhibits conversion of squalene to lanosterol and cholesterol trafficking

Question 18

Cholic acid forms what

Answer 18

Cholyl CoA pKa 6

Question 19

Cholyl CoA + taurine makes

Answer 19

Taurocholic acid pKa 2

Question 20

Cholyl CoA + glycine =

Answer 20

Glycoholic acid pKa 4

Question 21

Gallstones lead to what chronic issues

Answer 21

Malabsorption syndromes and deficiencies in fat soluble vitamins

Question 22

Which CYP are responsible for drug metab

Answer 22

1,2, 3

Question 23

Inhibiting CYPs causes an increase in statins which can lead to

Answer 23

Myopathy and rhabdomyolysis

Question 24

What are some inhibitors in CYP

Answer 24

Itraconozole, clarithromycin, and cyclosporine, citrus

Question 25

What are some CYP inducers

Answer 25

Rifampicin, carbamazepine, St John’s wort

Question 26

What does the liver store in excess

Answer 26

Glucose, vitamin A, vitamin D, iron

Question 27

What is the toxic byproduct of chloramphenicol

Answer 27

Aniline

Question 28

IPP can be converted to

Answer 28

tRNA

Question 29

Farnesyl PP is conververed to

Answer 29

Dolichol - protein glycosylation Ubiquinone Heme A RAS

Question 30

What processes are interrupted by statins

Answer 30

tRNA synth Protein glycosylation CoQ, electron transport RAS

Question 31

What inhibits squalene synthase

Answer 31

Lapaquistat

Question 32

What is the toxic intermediate produced by acetaminophen

Answer 32

NAPQI

Question 33

What is the rate limiting step of bile salt synthesis

Answer 33

Cholesterol to 7α hydroxycholesterol by 7α hydroxylase

Question 34

What inhibits 7a hydroxylase? Stimulates

Answer 34

Bile acids; cholesterol

Question 35

What inhibits recycling of bile salts

Answer 35

Cholestyramine

Question 36

What causes statin myopathy

Answer 36

Depletion of ubiquinone (CoQ10) and resultant impairment of mitochondrial function

Question 37

Inhibitors of squalene synthase should ______ levels of CoQ10 in muscles

Answer 37

Increase