Phase 2 conjugation reactions

Question 1

What are the 6 types of phase 2 Conjugation reactions

Answer 1

1-Glucuronidation
2-Sulfation
3- Amino acid Conjugation
4-Glutathione conjugation
5- Acetylation
6-Methylation

Question 2

True or False: Glucuronidation is the most common pathway?

Answer 2

True

Question 3

What enzyme is involved Glucuronidation

Answer 3

UGT

Question 4

What co-factor is involved in glucuronidation

Answer 4

UDPGA (UDP-glucuronic acid)

Question 5

What are the targets in glucuronidation

Answer 5

-OH, -COOH- NH2, SH

Question 6

What is the outcome of glucuronidation?

Answer 6

Forms β-D-glucuronides, increases polarity → easier renal/biliary excretion

Question 7

State the 2 steps in Glucuronidation

Answer 7

1- the synthesis of UDPGA
2- the transfer of glucuronic acid to drug

Question 8

What type of reaction is the transfer of glucuronic acid to drug

Answer 8

Nucleophilic substitution with inversion

Question 9

What enzyme is involved in Sulfation

Answer 9

Sulfotransferase

Question 10

What co-enzyme is involved in sulfation

Answer 10

PAPS

Question 11

What does sulfation target?

Answer 11

phenols, alcohols, amines and thiols

Question 12

what tissues does sulfation target

Answer 12

Liver, kidney and intestine

Question 13

What’s the outcome of sulfation?

Answer 13

Adds SO^3- group increasing solubility

Question 14

State the steps involved in sulfation

Answer 14

1- synthesis of PAPS to ATP + sulfate
2- Transfer of SO^3- to substrate

Question 15

What enzyme is involved in amino acid conjugation

Answer 15

Amino acid transferase

Question 16

What cofactors are involved in amino acid conjugation

Answer 16

Acetyl-CoA & ATP

Question 17

What is targeted during amino acid conjugation

Answer 17

Carboxylic acids

Question 18

What amino acids are used in amino acid conjugation

Answer 18

Glycine, glutamine, taurine, histidine

Question 19

What is the outcome of amino acid conjugation

Answer 19

Amide formation

Question 20

What steps are involved in amino acid conjugation

Answer 20

-Activation of -COOH
2- Conjugation with amino acid

Question 21

What enzyme is involved in Glutathione conjugation

Answer 21

Glutathione S-transferase

Question 22

What co-factor is involved in glutathione conjugation

Answer 22

GSH

Question 23

What are the targets for glutathione conjugation

Answer 23

Electrophilic centres (epoxides and halides)

Question 24

What is the function of glutathione conjugation

Answer 24

Detoxification- preventing cellular damage

Question 25

Outcome of glutathione conjugation

Answer 25

Non-toxic adduct excreted after modification

Question 26

What enzyme is involved in acetlyation

Answer 26

N-acetyltransferase

Question 27

what cofactor is involved in acetylation

Answer 27

Acetyl-CoA

Question 28

Targets in acetylation

Answer 28

aromatic amines, sulfonamides and hydrazines

Question 29

Outcome of acetylation

Answer 29

Decreases polarity forming an amide

Question 30

What enzyme is involved in methylation

Answer 30

Methyltransferase

Question 31

Cofactor in methylation

Answer 31

SAM

Question 32

Targets in methylation

Answer 32

Phenols, amines, thiols , N-heterocycles

Question 33

Outcome of methylation

Answer 33

decreased polarity inactivating the drug

Question 34

What is the pathway in methylation

Answer 34

Methionine → SAM → Methyl group transferred → SAH