Liver Biochemistry

Question 1

What is the blood supply to the liver?

Answer 1

75% supplied by portal vein

25% supplied by hepatic artery

Question 2

How does bile flow in the liver in regard to blood flow?

Answer 2

Opposite of blood flow

Question 3

What is the purpose of Kupffer cells in the liver?

Answer 3

They are macrophages that protect the liver from microbes

Question 4

What are the functions of the liver?

Answer 4

Carbohydrate metabolism (glycogen synthesis, glycogenolysis, gluconeogenesis)

Lipid Metabolism

Removal of nitrogen

Protein and AA metabolism

Bilirubin metabolism

waste management

Question 5

What are some important structural features of the liver?

Answer 5

Fenestrations in edonthelial cell membrane to allow increased contact between liver and blood

Question 6

Describe the four steps in the emulsification of bile salts

Answer 6

1) Bile acid ionizes to become a bile salt
2) Hydrophobic surface of bile salt associates with TAG to become a micelle
3) Hydrophilic surface of bile salt faces outward so it can associate with pancreatic lipase
4) Lipase frees FA to assoicate in a smaller micelle that is absorbed through intestinal mucosa

Question 7

What is the rate limiting enzyme in the synthesis of bile?

Answer 7

7 alpha-hydroxylase in the conversion of cholesterol to 7 alpha-hydroxycholesterol

Question 8

How many hydroxyl groups does chenodeoxycholic acid have?

How many does cholic acid have?

Answer 8

2 hydroxyl groups

3 hydroxyl groups

Question 9

What is the purpose of adding taurine and glycine to cholyl CoA?

Answer 9

To lower the pKa, the more ionized the molecule, the better the detergent effect

Question 10

What are the two end results of the bile salts after leaving the bile duct?

Answer 10

Excreted in feces (5%)

Recycled to the liver via enterohepatic circulation (95%)

Question 11

What are the two secondary bile acids and what are they derived from?

Answer 11

deoxycholic acid derived from cholic acid

lithocholic acid derived from chenodeoxycholic acid

Question 12

How does cholestyramine lower plasma cholesterol levels?

Answer 12

Cholestyramine binds to bile acids and since cholestramine cannot be reabsorbed it is excreted

Question 13

What are gallstones made of?

Answer 13

BIle supersaturated with cholesterol

Question 14

What can cause cholelithiasis?

Answer 14

Insufficient secretion of bile salt or excess cholesterol secretion into bile

Question 15

What are metabolites and what are xenobiotics?

Answer 15

Metabolites are compounds made in the body

Xenobiotics are compounds ingested from outside with no nutritional value

Question 16

What are the two steps in detoxification of xenobiotics?

Answer 16

Phase I-polarity is increased (Catalyzed by Cytochrome P450)

Phase II- Functional groups are conjugated for safe excretion

Question 17

Describe the reaction sequence of Ctyochrome P450

Answer 17

1) P450 attached to drug with ferric heme
2) P450 Reductase changes ferric to ferrous
3) O2 is added
4) 2H+ is added and the drug is now hydroxylated

Question 18

If an agent inhibits CYP, how does that affect drug levels in the plasma?

Answer 18

Increase in drug levels

Question 19

What are some CYP inhibitors and CYP inducers?

Answer 19

CYP inhibitors- citrus juices, grapefruit juice

CYP inducers-St. Johns Wort, rifampicin, carbamazepine

Question 20

What happens when a person takes too much acetaminophen?

Answer 20

Capacity for normal conjugation is overwhelmed which creates free radicals

treated by giving N-acetyl cysteine

Question 21

What is one thing all diseases of the liver have in common?

Answer 21

There is impairment of free exchange of material between hepatocytes and blood due to a buildup of collagen

Question 22

How does liver disease affect ALT and AST?

Answer 22

Serum activity of ALT and AST increases