4. Drug Metabolism 2 - Phase Ii

Front 1

What happens in PHase II metabolism reactions?

Back 1

Conjugation of an endogenous chemical group to a drug or drug metabolite

Front 2

What are 4 major types of conjugation reactions in Phase II metabolism?

Back 2

-Glucuronidation
-Acetylation
-Sulfation
-Glutathione conjugation

Front 3

In what order do the metabolism reactions occur?

Back 3

Any order - depends on the drug and its functional groups and available enzymes

Front 4

What is required of the endogenous chemical group in order for conjugation to occur?

Back 4

It must be a High Energy intermediate

Front 5

What is the high E intermediate for:
-Glucuronidation
-Acetylation
-Sulfation
-GSH conjugation

Back 5

Glucur - UDP-glucuronic acid
Acetyln - Acetyl-CoA
Sulfation - PAPS
-GSH conj - The drug itself

Front 6

What enzyme catalyzes Glucuronidation? Where is it located?

Back 6

UDP-glucuronosyl transferases UGT - in ER lumen

Front 7

What enzyme catalyzes Acetylation? Where is it located?

Back 7

N-acetyltransferase - in the cytosol

Front 8

What enzyme catalyzes Sulfation? Where is it located?

Back 8

Sulfotransferase (SULT) - in the cytosol

Front 9

What enzyme catalyzes Glutathione conjugation? Where is it located?

Back 9

Glutathione S-transferase (GST)
-In the cytosol and some ER

Front 10

What is the nature of metabolies generated by Phase II reactions?

Back 10

-More polar
-Inactive or less toxic

Front 11

What are the 2 exceptions to drug metabolites of Phase II reactions being more polar?

Back 11

-Acetyltransferases
-Methyltransferases
These metabolites can be LESS polar!

Front 12

What is the substrate specificity of Phase II enzymes like?

Back 12

Broad - enzymes look for functional groups

Front 13

What are some phase II enzymes?

Back 13

Inducible

Front 14

What are the kinetics of phase II enzymes?

Back 14

Conventional michaelis menton

Front 15

What is the Vmax of phase II enzymes limited by?

Back 15

-Supply of conjugation materials
-Conventional enzyme kinetics

Front 16

What induces an inducible enzyme?

Back 16

Increasing drug concentration (substrate)

Front 17

What type are most conjugation reactions catalyzed by?

Back 17

UDP-glucuronosyltransferase (UGT)

Front 18

Do phase II enzymes only act on drugs?

Back 18

No they can also act on endogenous compounds

Front 19

For which type of conjugation reaction is there
-High capacity
-High raw material supply

Back 19

Glucuronidation (UGT)

Front 20

For which type of conjugation reaction is there
-Variable capacity
-Variable raw material supply

Back 20

Acetylation

Front 21

For which types of conjugation reactions is there
-Low capacity
-Low raw material supply

Back 21

-Sulfation
-Glutathione conjugation