Phase 1 biotransformation

Question 1

what is the main principle of biotransformation

Answer 1

conversion of compounds from lipophilic (non-polar) to hydrophilic (polar) followed by excretion in urine or bile

Question 2

what are the three types of phase 1 reactions

Answer 2

1. hydrolysis
2. reduction
3. oxication

Question 3

what is hydrolysis reaction

Answer 3

exposes or introduces a functional group

Question 4

what is reduction reaction

Answer 4

adds an OH, Nh2, Sh, COOH

Question 5

what is an oxidation reaction

Answer 5

adds COO- to become water soluble

Question 6

what is needed for phase 2 reaction to happen

Answer 6

the new functional group added to the molecule must be nucleophilic or electrophilic

Question 7

what is the main liver form of carboxyesterases, what does it do

Answer 7

CES1

- hydrolyzes xenobiotics with small alcohol leaving groups

Question 8

what is the main intestinal form of carboxylesterases

Answer 8

CES2

- hydrolyzes xenobiotics with large alcohol leaving groups

Question 9

what are three examples of cholinesterase’s

Answer 9

1. acetylcholinesterase
2. AChE inhibitors as therapeutics
3. Organophosphates

Question 10

what moieties can a xenobiotic have that can be reduced in vivo

Answer 10

aldehyde, ketone, disulfide, sulfoxide, quinone

Question 11

what happens in a carbonyl reduction

Answer 11

carbonyl moieties (R-CHO and R1-CO-R2) reduced by carbonyl reductase

Question 12

what happens with aldehyde dehydrogenase

Answer 12

oxidation of xenobiotic aldehydes formed from alcohol and non-alcohol molecules

Question 13

what inhibits acetaldehyde dehydrogenase

Answer 13

disulfiram (antabuse)

Question 14

what does monoamine oxidase do? (MAOA, MAOB)

Answer 14

oxidative deamination of primary, secondary, and tertiary amines

Question 15

what enzyme metabolizes serotonin and chatecholamines

Answer 15

monoamine oxisase

Question 16

what do CYP enzymes transform acetaminophen into

Answer 16

NAPQI

Question 17

what are three things that reduce CYP activity

Answer 17

1. genetic mutations
2. environmental factors line infection or inflammation
3. a xenobiotic that inhibits or competes with CYP

Question 18

what are four things that increase CYP activity

Answer 18

1. gene duplication
2. gene mutation in promoter region
3. a xenobiotic that increases activity of existing CYP protein
4. a xenobiotic that increases expression of a CYP

Question 19

describe sex differences in xenobiotic metabolism

Answer 19

• large in some rodents, lower for humans

- idiosynchratic drug reactions are more frequent in females

Question 20

explain the interplay between intraconazole and carbamazepine and CYP3A4

Answer 20

intraconazole: anti-fungal that inhibits CYP3A4
Carbamazepine: anti-convulsant that induces CYP3A4