Reactions and their enzymes/co-substrates

Question 1

Aromatic ring hydroxylation

Answer 1

CYP450 + NADPH-CYP450 reductase

Need NADPH, H+, and O2

Question 2

Aliphatic hydroxylation

Answer 2

CYP450 + NADPH-CYP450 reductase

Need NADPH, H+, and O2

Question 3

N-Dealkylation

Answer 3

CYP450 + NADPH-CYP450 reductase

Need NADPH, H+, and O2

Question 4

O-dealkylation

Answer 4

CYP450 + NADPH-CYP450 reductase

Need NADPH, H+, and O2

Question 5

N and S oxidation

Answer 5

CYP450 + NADPH-CYP450 reductase

Need NADPH, H+, and O2

Question 6

Epoxidation

Answer 6

CYP450 + NADPH-CYP450 reductase

Need NADPH, H+, and O2

Question 7

Dehalogenation

Answer 7

CYP450 + NADPH-CYP450 reductase

Need NADPH, H+, and O2

Question 8

Desaturation

Answer 8

CYP450 + NADPH-CYP450 reductase

Need NADPH, H+, and O2

Question 9

Oxidation of N, S, and P

Answer 9

Flavin monooxygenase

Cofactors: NADPH, O2

Question 10

Converting alcohols to aldehydes

Answer 10

Alcohol dehydrogenase

Cofactors: NADPH, O2

Question 11

Converting aldehydes to carboxylic acids

Answer 11

Aldehyde dehydrogenase

Cofactors: NADPH, O2

Question 12

Oxidizing primary amines (2 carbons away from phenyl), pyridine

Answer 12

Monoamine oxidase

Cofactors: NADH, O2

Question 13

Oxidizing xanthine like structures

Answer 13

Xanthine oxidase (NADH, O2)

Question 14

Hydrolyze ester bonds

Answer 14

Esterase, need water

Question 15

Hydrolyze amide bonds

Answer 15

Amidase, need water

Question 16

Hydrolyze peptide bonds

Answer 16

Peptidase, need water

Question 17

Hydrolyze epoxides

Answer 17

Epoxide hydrolase, need water

Question 18

Reduce nitro groups to amino groups

Answer 18

Nitroreductase, need NADPH

Question 19

Reduce azo groups to amino groups

Answer 19

Azoreductase, need NADPH

Question 20

Add glucuronic acid (5 targets) to a substrate

Answer 20

UGT, cosubstrate: UDP-glucuronic acid (UDPGA)

Targets: Hydroxyl groups (ali and aro)
Carboxylate groups
Thiols
Amines
Nucleophilic carbons

Question 21

Add sulfonic acid to a substrate (2 targets)

Answer 21

Sulfonation
SULT, cosub: PAPS
Hydroxyl groups, amines

Question 22

Add a glutathione conjugate to a substrate (4 targets)

Answer 22

Glutathione conjugation
GST, cosub: GSH
Targets: Alkyl halides, some aryl halides, alpha beta unsaturated ketones, epoxides

Question 23

Add acetyl group to a substrate (1 target)

Answer 23

Acetylation
NAT, cosub: acetyl co-enzyme A
Target: Amines (typically primary)

Question 24

Add an amino acid (1 target)

Answer 24

step 1: Acyl-coenzyme A ligase
Step 2: Acyl-CoA-amino acid N-acyltransferase

Cosub: typically glycine (N-CH2-COOH), sometimes glutamine or taurine

Target: carboxylic acids

Question 25

Add a methyl group to catechols

Answer 25

O-methylation:
Catechol o-methyltransferase with cosubstrate SAM

Targets: drugs with catechol groups (two alcohols on a phenyl ring)

Question 26

Add a methyl group to thiols

Answer 26

S-methylation
TPMT, cosubstrate SAM

Target: thiol groups

Question 27

Adding a fatty acid

Answer 27

Fatty acid conjugation
Ester hydrolase with cosubstrate: fatty acid
Targets: alcohol halides, p-aminophenols

Question 28

Adding a cholesterol

Answer 28

Cholesterol ester formation
Ester hydrolase with cosubstrate: cholesterol
Targets: acid halides

Question 29

Transporting neutral, bulky, or weakly cationic drugs out of the cell

Answer 29

ABC superfamily
MDR1 (p-glycoprotein)

(Multi drug resistance)

Question 30

Transporting anions out of the cell

Answer 30

ABC superfamily
MRP2

(Multi drug resistance)

Question 31

Transporting glycine conjugates to the blood from kidney tubules through anion exchange

Answer 31

SLC superfamily (no atp required)
OAT1 (organic anion transporters)