Exam II: CYP450/Phase I Enzymes

Question 1

which CYP enzymes are inducible?

Answer 1

CYP1, CYP2, CYP3, and CYP4

Question 2

example of CYP enzyme not inducible?

Answer 2

CYP2D6

Question 3

abbrevation difference for cyps between humans and animals?

Answer 3

humans are uppercase (CYP450)

animals are lowercase (cyp450)

Question 4

most important CYPs for xenobiotic metabolism?

Answer 4

CYP2C, CYP2D6 and CYP3A4/5

Question 5

CYPs responsible for activation of many protoxins and procarcinogens

Answer 5

CYP1A, CYP1B, CYP2A, CYP2B and CYP2E

Question 6

CYP accountable for metabolism of almost 50% of drugs

Answer 6

CYP3A4

Question 7

where in the cell are P450 enzymes found?

Answer 7

ER

Question 8

list the CYP-mediated rxns

Answer 8

Aliphatic hydroxylation
Aromatic hydroxylation 
Epoxidation
N-dealkylation
O-dealkylation
Oxidative deamination
N-oxidation
S-oxidation
Alcohol oxidation
Phosphothionate oxidation

Question 9

explain aliphatic hydroxylation

Answer 9

oxidation occurs on a saturated carbon (alkane)

CH3 group is oxidized into C-OH

Question 10

explain allylic hydroxylation

Answer 10

oxidation occurs on a carbon directly adjacent to a carbon-carbon double bond
also CH3 group is oxidized into C-OH

Question 11

what cofactors are necessary for biotransformation of drugs by CYP450?

Answer 11

NADPH and oxygen

Question 12

what is NADPH-P450’s role in electron transport chain?

Answer 12

primary source of electrons -> it donates electrons

Question 13

explain benzylic hydroxylation

Answer 13

OH group added to carbon right next to ring
typically methyl (CH3) or methylene (CH2)

Question 14

explain aromatic ring hydroxylation

Answer 14

OH group added to para position of benzene ring

Question 15

rank from most likely to react to least likely to react for hydroxylation (para,meta,ortho)

Answer 15

para > ortho > meta

Question 16

explain aliphatic double bond oxidation

Answer 16

enzyme breaks C to C double bond forming an epoxide which reacts to become OH group

Question 17

explain N-demethylation

Answer 17

methyl group attached to N is removed leaving NH

Question 18

explain O-dealkylation

Answer 18

group attached to O removed leaving OH

Question 19

heteroatom dealkylation is initiated by HAT or SET? what is formed?

Answer 19

HAT, forms a neutral carbon radical intermediate

Question 20

heteroatom oxygenation is initiated by HAT or SET? what is formed?

Answer 20

SET, forms a radical carbon intermediate

Question 21

N-dealkylation occurs HAT or SET?

Answer 21

both

Question 22

N-oxidation occurs HAT or SET?

Answer 22

SET

Question 23

O-dealkylation occurs HAT or SET?

Answer 23

HAT

Question 24

what does FMO utilize?

Answer 24

NADPH

Question 25

what element does FMO not oxidize?

Answer 25

carbon

Question 26

which FMO is most important for drug metabolism? (FMO1, FMO2, FMO3)

Answer 26

FMO1

Question 27

FMOs are similar to what other enzyme?

what do they do?

Answer 27

CYP450s

oxidizes, usually N or S

Question 28

what does MAO utilize?

Answer 28

FAD

Question 29

two forms of MAO?

Answer 29

MAO-A and MAO-B

Question 30

unlike CYP enzymes, for MAO, oxygen in the product comes from ____ instead of __

Answer 30

H2O, O2

Question 31

what does oxidation of MAO look like?

Answer 31

does deamination (NH3 to NH2) forming an imine intermediate which is hydrolyzed into an aledehyde

Question 32

explain sulfoxide reduction

Answer 32

replaces oxygen bound to S with a hydrogen

ex. S double bond O -> S bond to H

Question 33

2 enzymes in quinone reductase?

Answer 33

QR1 and QR2

Question 34

two products of ester hydrolysis?

Answer 34

alcohol and carboxylic acid