Drug Metabolism Pathways (DM13)

Question 1

All of the following are correct attributes of DM and DMEs, except:
A.  Xenobiotic inactivation
B. Microsomal activity
C. Hepatocyte inactivity
D. Nuclear receptor activation

Answer 1

C. Hepatocyte inactivity

Question 2

Phase 1 pathways include what enzymes?

Answer 2

CYP450 & Non-CYP450
ADH
ALDH
XO
MAO
FMO
Azo-reductase
Nitro-reductase
cytosolic enzymes
EH
3A4
Carboxyesterases

Question 3

Phase 1 pathways include what reactions?

Answer 3

Oxidations (Use CYP450 & Non-CYP450)
Reductions
Hydrolytic

Question 4

Phase 1 reactions are functionalization meaning?

Answer 4

New FGs are introduced or existing FGs are modified or exposed in readiness for excretion or conjugation.

Question 5

What are the types of reactions included in CYP450 oxidative reactions?

Answer 5

Aliphatic, allylic & benzylic carbons
Aromatic groups
Heteroatom systems (N-dealkylation, N-oxidation, O-dealkylation, S-dealkylation, Oxidative deamination_
Dehalogenation
Epoxidation

Question 6

What are the types of Non-CYP450 oxidations?

Answer 6

ADH, ALDH, Xanthine oxidase, MAO, FMO

Question 7

What are the types of reductive reactions?

Answer 7

Azo, Nitro, Miscellaneous reductive reactions

Question 8

What are the types of hydrolytic reactions?

Answer 8

Esters, Amides, Epxoides

Question 9

\_\_\_\_\_\_\_\_ are the only exception to the commonly encountered reactions of the phase I type.
A.  Bond reductions
B. Bond hydrolysis
C.  O-atom additions
D. N-atom additions

Answer 9

D. N-atom additions

Question 10

What does Alcohol Dehydrogenase (ADH) do and what pathway is it part of?

Answer 10

It changes primary alcohols to aldehydes in the liver. It is part of the Non-CYP450 Oxidations.

Question 11

What type of specific enzyme is ADH and ALDH?

Answer 11

NAD

Question 12

What does Aldehyde Dehydrogenase (ALDH) do and what pathway is it part of?

Answer 12

It changes aldehydes to Carboxylic acids in the liver (mitochondrial). It is part of the Non-CYP450 Oxidations.

Question 13

What does Xanthine Oxidase/Dehydrogenase or Xanthine Oxidoreductase do?

Answer 13

Purine metabolism in the liver and intestine.

Question 14

What is the cofactor of Monoamine oxidase (MAO)?

Answer 14

Flavin Adenosine Dinucleotide (FAD)

Question 15

What does MAO do?

Answer 15

Neurotransmitter metabolism in the mitochondiral

Question 16

What does Flavin-containing Monooxygenase (FMO) do?

Answer 16

Uses reduced flavin to activate molecular oxygen in microsomal.

Question 17

What does FMO require?

Answer 17

FMN(flavin mononucleotide) reductase

Question 18

What does FMO oxidate?

Answer 18

amines & thiols (3 amines and amides from N-oxides)
1 & 2 amines form hydroxylamines
thiols form sulfoxides and sulfones

Question 19

Azo-reductase is what type of reaction?

Answer 19

Reduction reaction in intestinal microflora

Question 20

What miscellaneous reductions occur by cytosolic enzymes?

Answer 20

Disulfirm to Diethyldithiocarbamic Acid

Dimethylsulfoxide to Dimethylsulfide

Question 21

In hydrolytic reactions epoxide hydrolysis occurs by what enzyme?

Answer 21

Epoxide hydrolases (EH)

Question 22

In hydrolysis reactions ester hydrolysis and amide hydrolysis occurs by what enzyme?

Answer 22

Carboxyesterases

Question 23

What enzyme is not a member of the phase I family?
A. 3A4
B. NAT
C. FMO
D. EH
E. MAO

Answer 23

B. NAT

Question 24

What are the phase 2 pathways?

Answer 24

Conjugation or synthesis
utilize existing Functional Groups
Most increase polarity for urinary excretion
Other decrease polarity
Catalyzed by enzymes known as transferases
Require an endogenous cofactor

Question 25

What are the phase 2 reactions?

Answer 25

``` Glucuronidation Sulfation Glutathione Conjugation Acetylation Amino Acid Conjugation Methylation ```

Question 26

What is the enzyme for glucuronidation?

Answer 26

UGT (Uridine diphosphate glucuronosyl transferase)

Question 27

What is the enzyme for sulfation?

Answer 27

SULT (Sulfotransferase)

Question 28

What is the enzyme for Glutathione Conjugation?

Answer 28

GST (Glutathione S-transferase)

Question 29

What is the enzyme for Acetylation?

Answer 29

NAT (N-ACetyltransferase)

Question 30

What is the enzyme for Amino acid conjugation?

Answer 30

Acylsnthatase

Question 31

What is the enzyme for Methylation?

Answer 31

Methyltransferase (FG specific COMT, TPMT, PNMT, HMT)

Question 32

What are the substrates of Glucuronidation?

Answer 32

``` Alcohols & Phenols Carboxylic Acids Aromatic Amines Thiols Bilirubin ```

Question 33

What are the substrates of Sulfotransferases?

Answer 33

Phenols, Alcohols, and Aromatic amines

Question 34

What is the cofactor of UGT?

Answer 34

UDPGA

Question 35

What is the cofactor of ST or SULTs?

Answer 35

PAPS

Question 36

What is the cofactor of GST?

Answer 36

GSH

Question 37

What are the target FGs of Glutathione S-transferase?

Answer 37

Electrophilic centers: Halides, Epoxides, and other electrophiles.

Question 38

What are the target FGs of Acetylation?

Answer 38

Amine, Hydrazines, and Sulfonamides.

Question 39

What is the cofactor of NAT?

Answer 39

Acetyl-CoA

Question 40

In amino acid conjugation Acyl Synthetase requires what to activate the target FG?

Answer 40

Acetyl Coenzyme A

Question 41

What are the target FGs of Acyl Synthetase?

Answer 41

Aromatic COOH, Aliphatic COOH, Heterocyclic COOH.

Question 42

What are the target FGs of Methyl transferases?

Answer 42

OH, -NH2, Heterocyclic-N, -SH

Question 43

What is the cofactor of methyl transferases?

Answer 43

SAM

Question 44

What are the NAD specific enzymes?

Answer 44

ADH & ALDH

Question 45

What is the cofactor for MAO reactions?

Answer 45

Flavin Adenosine Dinucleotide (FAD)

Question 46

What are the reduction reaction's enzymes?

Answer 46

Azo-reductase Nitro-reductase Miscellaneous reductions by cytosolic enzymes

Question 47

What are the hydrolytic reactions?

Answer 47

Epoxide hydrolysis Ester hydrolysis Amide hydrolysis