Lecture 11- Phase II metabolism 1

Question 1

Give an example of a conjugation reaction

Answer 1

Sulfation
Glucuronidation

Question 2

give the enzymes used for Glucuronidation and sulfation

Answer 2

Glucuronidation- UDP-GT sulfation- Sulfotransferase

Question 3

what reactions are phase 2 metabolism

Answer 3

conjugation reactions

Question 4

Give the characterisics of conj reCTIONS?

Answer 4

compounds have greater molecular weight and are more water soluble
Less able to pass through cell membranes
easier to excrete

Question 5

Phase II metabolism usually results in ________, though there are exceptions

Answer 5

detoxification

Question 6

what is the most widely used phase 2 reaction?

Answer 6

glucuronidation

Question 7

what is required as a cofactor for glucuronidation reactions?

Answer 7

UDP-glucuronic acid

Question 8

________ compounds such as steroids, vitamins, bile acids and
bilirubin also undergo conjugation by UDPGTs

Answer 8

Endogenous

Question 9

describe properties of UDP-GTs ?

Answer 9

• found in endoplasmic reticulum (luminal face)
• monomeric proteins of molecular weight 50 to 60,000
• no prosthetic group
• highest levels found in liver- also present in kidney, lung, small intestine skin and adrenal gland

Question 10

what does glucuronic acid conjugation promot

Answer 10

excretion and results
in loss of biological activity

Question 11

which glucuronides hVE biological activity ?

Answer 11

morphine
glucuronide

Question 12

Some glucuronides, like morphine glucuronide, still work in the body even after being changed for excretion. Other glucuronides, like acyl glucuronides, can stick to proteins in cells and cause damage, which might lead to an immune reaction or allergic response.

Question 13

what are the 2 human UDP-GT families ?

Answer 13

UGT1 and UGT2
at least 10 different UGT1 isoforms but all products of same gene
-Single variable isoform specific exon (exon 1) and 4 common exons (2 to 5)