L25 - Liver Function - Metabolism

Question 1

How do molecules reach the liver? What type of molecules?

Answer 1

Through the hepatic artery and portal vein
- endogenous and ingested molecules and compounds

Question 2

What happens to the molecules when they reach into the liver?

Answer 2

Some are secreted into bile, most reabsorbed in the SI

Question 3

What molecules are metabolised by liver enzymes?

Answer 3

Lipophilic molecules (and drugs)
- to form polar products excreted in the urine

Question 4

What are the two stages to the metabolism?

Answer 4

• phase I
• phase II

Question 5

What are reactions and products like during phase I?

Answer 5

Catabolic - oxidation, reduction or hyrdolysis
Product - still or even more reactive

• mainly applicable to lipid soluble molecules (has to enter cells)

Question 6

What happens during phase I reactions?

Answer 6

Introduces a functional group - provide point of conjugation

Question 7

What are reactions carried out by in phase I?

Answer 7

Hepatic microsomal enzymes (found in ER inside hepatocytes)

Question 8

What is the main microsomal enzyme from?

Answer 8

Cytpchrome P450 family (CYP enzymes)

Question 9

What is the (CYP) Cytochrome P450 monooxygenase system?

Answer 9

• family of haem enzymes
• different members of the family

Question 10

What do cytochrome P450 enzymes differ in?

Answer 10

• a/a seq
• substrate specificity
• susceptibility to inducers and inhibitor

Question 11

What does variations in expression and polymorphic forms of CYP enzymes result in?

Answer 11

Species and inter-individual variation

-important implications in drug testing and drug response

Question 12

What is the monooxygensae P450 cycle?
FINISH

Answer 12

• P450 w/ Fe3+ combines with drug
• e- from NADPH P450 reductase
• Fe reduced to Fe2+
• combines w/ O2, proton and 2nd e-
  = FeOOH-DH
• combines w/ proton = water and FeO3+DH