Metabolism: Liver Metabolism

Question 1

What is cytochrome p450?

Answer 1

superfamily of enzymes used in drug metabolism

- oxidizes drugs and organic metabolites

Question 2

What is the requirement for drug excretion via the kidney?

Answer 2

drug must be hydrophilic

Question 3

In general, describe the metabolism of a drug by cytochrome p450.

Answer 3

1. NADPH => NADP via NADPH-cytochrome-p450-reductase
2. electron added to drug-cytochrome complex
3. drug is now reduced
4. add O2, H
5. drug is now oxidized
6. drug and cytochrome separate
7. oxidized drug includes OH/COOH (hydrophilic components)

Question 4

Under what conditions do drug metabolism enzymes have decreased activity?

Answer 4

• newborns
• elderly
• undernutrition

Question 5

Under what conditions do drug metabolism enzymes have increased activity?

Answer 5

• smoke induces polyclyclic aromatic hydrocarbons

Question 6

What is the purpose of phase 2 drug metabolism reactions?

Answer 6

conjugate oxidized drug products to make them more hydrophilic
- ex: glucuronate, glycine, taurine, sulfate

Question 7

What is the purpose of plasma proteins?

Answer 7

• plasma oncotic pressure maintenance
• conjugation of bilirubin
• FA transport

Question 8

How is vitamin A transported to the liver?

Answer 8

• exists as retinol esters in chylomicrons
• LPLs breakdown chylomicrons to chylomicron remnants
• delivered to liver

Question 9

How does the liver maintain vitamin A homeostasis?

Answer 9

• breaks down stored retinyl esters to retinol
• association with retinol-binding-protein (RBP)
• released into circulation

Question 10

How much vitamin A is stored?

Answer 10

80% stored in liver

Question 11

How is vitamin D transported?

Answer 11

• chylomicrons

- vitamin D3 (nonesterified calcitriol)

Question 12

Where are vitamin D stores found?

Answer 12

adipose

skeletal muscle

Question 13

What is the liver’s role in vitamin D metabolism?

Answer 13

• activates D3 via hydroxylation => 25-hydroxycholecalciferol
• synthesizes vitamin-D binding protein (DBP) which binds to D3

Question 14

Where is vitamin K found in the body?

Answer 14

• stored in skeletal muscle

- required in liver for prothrombin synthesis

Question 15

List the steps to make the stored form of iron.

Answer 15

1. dietary iron binds to transferrin protein transporter
2. transferrin-Fe binds to transferrin receptor on liver and is endocytosed
3. heme oxygenase breaks down to release free iron into the free iron pool
4. iron stimulates synthesis of ferritin (stored form)

Question 16

What is the free iron pool in the liver used for?

Answer 16

• synthesis of apotransferrin protein
• synthesis of transferrin
• ferritin

Question 17

What are the sources of the iron pool?

Answer 17

• heme degradation

- dietary Fe

Question 18

What is the liver’s role in copper metabolism?

Answer 18

• storage

- excretion in bile

Question 19

List the hormones that liver metabolism is involved with.

Answer 19

• D3
• thryoid
• IGF

Question 20

Describe the liver’s role in D3 activation.

Answer 20

takes D3 and hydroxylates it

Question 21

Describe the liver’s role in thyroid hormone activation.

Answer 21

converts T4 to T3

Question 22

Describe the liver’s role in IGF hormone activation.

Answer 22

• synthesis of Insulin-like Growth Factor

- stimulated by somatotropin