Non Cyp Phase 1

Question 1

What enzymes cause oxidation reactions

Answer 1

Flavin linked monooxygenases (FMO)
Prostaglandin H synthase dependent co oxidation
Amine oxidase
Oxidoreductase

Question 2

What enzymes cause hydrolysis

Answer 2

Esterases
Epoxide hydrolases

Question 3

Where are FMOs found

Answer 3

ER

Question 4

What do FMOs oxidise

Answer 4

Nucleophilic N, P or S centres

Question 5

What does FMO require

Answer 5

NADPH, O2 and FAD prosthetic group

Question 6

FMO reaction mechanism

Answer 6

1. NADPH reduces FAD —> FADH2
2. O2 binds NAPD+-FADH2 complex
3. Forms FADH-OOH
4. Reacts with nucleophile substrate
5. One O is incorporated into substrate and the other into water
6. H2O and NADP+ is released

Question 7

How many isoforms of FMO is there

Answer 7

5 - show 50-55% identity with each other

Question 8

Give 2 examples of FMO catalysed reactions

Answer 8

N-deacetyl ketaconozole —> N-deacetyl-N-hydroxyketaconozole

Tamoxifen —> Tamoxifen-N-oxide

Question 9

Which FMO is found at high levels in the human liver

Answer 9

FMO3

Question 10

Which FMO is found in the human kidney

Answer 10

FMO1

Question 11

Which FMO is found in rat liver

Answer 11

FMO1

Question 12

Which FMOs are found in rat kidney

Answer 12

FMO1 FMO3 FMO4

Question 13

Explain the co-oxidation quality of PGHS

Answer 13

COX activity (arachidonic acid —> PGG2)
Peroxidase activity (PGG2 —> PGH2)

Question 14

What is PGHS’s role in paracetamol overdose

Answer 14

High doses of paracetamol can be converted to the toxic N-acetylquinoneimime in the kidney

Question 15

What do amine oxidases oxidise

Answer 15

Monoamine
Diamines
Polyamines

Question 16

What do MAOs

Answer 16

Metabolise neurotransmitters via FAD-dependent pathway

Question 17

Which MAO metabolises propranolol

Answer 17

MAOA

Question 18

Where are amine oxidases found

Answer 18

Mitochondria

Question 19

Describe metabolism of dopamine

Answer 19

DA -MOA-> X -ald dehydrogenase-> HVA

Question 20

4 oxidoreductases

Answer 20

Alcohol dehydrogenase
Aldehyde dehydrogenase
Carbonyl reductase
NAD(P)H quinone oxidoreductase

Question 21

What are oxidoreductases dependent on

Answer 21

NADP in the oxidising direction
NADPH in the reducing direction

Question 22

Where are oxidoreductases found

Answer 22

Cytosol

Question 23

What is the “normal” method of ethanol detoxification

Answer 23

Alcohol dehydrogenase
(CYP2E1 used excess ethanol as a substrate)

Question 24

Ethanol metabolism pathway

Answer 24

Ethanol -ADH-> acetaldehyde -AlDH-> carboxylic acid

Question 25

What plays a role in cyclophosphamide metabolism

Answer 25

Aldehyde dehydrogenase GSTs Alcohol dehydrogenase CYP2C9 CYP3A4

Question 26

What do carbonyl reductases do

Answer 26

Reduces quinones, prostaglandins, menadione

Question 27

Specific substrate of carbonyl reductase

Answer 27

Doxorubicin to doxorubicinol

Question 28

Why are quinone oxidoreductases important

Answer 28

Reduce quinones directly to hydroquinones without semiquinone intermediate by using 2 electrons instead of 1 - avoids generation of singlet oxygen

Question 29

Where are esterases found

Answer 29

Plasma and liver Cytosolic and microsomal forms

Question 30

4 types of esterase

Answer 30

Butyrylcholinesterase Carboxylesterase 1 Carboxylesterase 2 Paraoxonase

Question 31

What does cholinesterase metabolise

Answer 31

Aspirin

Question 32

What does CES1 metabolise

Answer 32

Cocaine / heroin

Question 33

What does CES2 metabolise

Answer 33

Procaine

Question 34

What does paraoxonase metabolise

Answer 34

Statins

Question 35

What do CES1 and CES2 prefer

Answer 35

CES1 - small OH group, large acyl group CES2 - larger OH group, small acyl group

Question 36

What do epoxide hydrolases do

Answer 36

Cleave epoxides in the presence of water

Question 37

Where are EPHs found

Answer 37

Cytosol and microsomes

Question 38

Epoxide hydrolase in benzoapyrene genotoxicity

Answer 38

BaP —(CYP1)—> B-epoxide —(EPH)—> B-diol —(CYP1)—> BPDE

Question 39

What does PON1 do

Answer 39

Protects LDL and HDL from lipid peroxidation