Phase I and II enzymes

Question 1

Phase I enzymes

Answer 1

Adds OH, does an oxidation

Question 1

Cytochrome P450 Superfamily

Answer 1

Smooth ER in liver cells (hepatocytes)

single non-selective enzymes

> 27000 P450 sequences

in many tissues

Requires NADPH

Polymorphic distribution (Extensive Metabilism, intermediate metabolism, poor and ultra rapid)

Question 2

Impact of Ke on bioavailability

Answer 2

Inhibition of metabilic enzymes (higher bio)

Inducers (lower bio)

PM ( Higher bio)

ULR (lower bio)

Question 3

Nomenclature

Answer 3

Gene and allele

Question 4

CYP1

Answer 4

Induced by PAH
Activate carcinogens

Includes CYP1 A
and CYP1 A2

Question 5

CYP1A

Answer 5

Substrate: PAH, Caffeine
Inducers: PAH, dioxins

Question 6

CYP1A2

Answer 6

Substrate: Acetominophen, caffein
Genotype: Polymorphisms are rare
Inducers: Brassica (brocoli fam), metabolites, charcoal grilled meats
Inhibited: Carrot fam: apiaceous

Question 7

CYP2 Family

Answer 7

Largest fam in humans
Can Hydoxylate steroids
Sex-specific expressed

Includes
B6, C9 and D6

Question 8

CYP2B6

Answer 8

Substrates: nicotine
Inhibitor: phenobarbital-type compounds
Expressed: liver, heart

Many different routes of metabolism

Question 9

CYP2C9

Answer 9

Substrates: Warfin
Genotype: liver, inestin

INDUCIBLE

2 conformations, dangerous to be a slow metaboliser

Question 10

CYP2D6

Answer 10

Substrate: SSRI
Genotype: liver, brain, heart

NON INDUCIBLE

Can inhibit itself

Question 11

CYP3 Family

Answer 11

CYP3A4 most abundant enzyme to metabolis drugs

Highly conserved but high inter-individual variability

Motly in liver but also intestin

Question 12

Epoxide Hydrates (hydrolases)

Answer 12

Epoxide is hydrolysed to make it more polar

Question 13

ADH

Answer 13

more then 6 genes contributing to 5 classes of dimeric ADH enxymes

ethanol to acetaldehyde by ADH

Question 14

ALDH

Answer 14

19 ALDJ genes
acethaldehyde to acetic acid by ALDH
acloohol flush reaction

Question 15

AChE

Answer 15

Reaction: Ester cleavage
Inhibitor: organophospharus xenobiotic
Target of alzeimers pharmacotherapy

Question 16

FMO

Answer 16

NOT Easily inducudes and inhibited
Different tissues and species acts different

Question 17

MAO

Answer 17

SubstrateL Monoamide neurotransmitter
Breaks down dopamine and trytptamine
Genotype: 2 types
1) MAO-A: in liver
2) MAO-B: mostly in blood palets

Ayahuasca (yagé): is a plant mixture and a good exemple of how different xenobiotics affect each other

Question 18

Phase II enzymes

Answer 18

Generally less active then parent but not alwasys

Question 19

Glutathione S-transferase M1

Answer 19

A glutathinone S-transferase group is TRANSFERED to xenobiotic making it more buly and polar

Question 20

N-Acetyltransferases (NAT)

Answer 20

Reaction product is more HYDROphobic. Catalyses the transfer of acetyl group from acetyl-coa

Question 21

COMT

Answer 21

Reaction: O-methylation of cathecholamines

Substrates: L-dopa and methyldopa

• A cytoplasmic form is predominly expressed in liver, intestine and kidney
• A membrane form is expressed in CNS

Question 22

Thiol methyltransferase

Answer 22

Reaction: S-methylation of aliphatic sulfhydryls
(membrane bound enzyme)

Substrates: xenobiotics thiols

Question 23

Thiopurine methyltransferase

Answer 23

Reaction: S-methyltransferase of aromatic and heterocyclic sulfhydryls (cytolasmic)

Substrates: xenobiotic thiopurines

Question 24

SULT

Answer 24

Rxn: SO3 from donar to form more hydrophilic
Substrate: non-peptide hirmones and may xenobiotics

Question 25

Uridine 5’-diphps^hate-glucuronosyltransferase

Answer 25

ADdoning a giant glucose group (D-gluronic acid) to increase polaritu