Non-CYP450 Mediated Reactions

Question 1

What enzyme catalyses alcohol oxidation?

Answer 1

Alcohol dehydrogenase

Question 2

What enzyme catalyses N and S-Oxidations?

Answer 2

Flavin Monooxygenase - FMO

Question 3

What enzyme catalyses oxidative deamination?

Answer 3

Monoamine oxidase - MAO

Question 4

What enzyme catalyses aldehyde oxidations?

Answer 4

Aldehyde oxidase

Question 5

How does Disulfiram work?

Answer 5

Disulfiram inhibits aldehyde dehydrogenase, resulting in worse hangovers

Used to treat alcohol abuse

Question 6

Where is Flavin monooxygenase found and what reactions does it mediate?

Answer 6

Found alongside P450s in liver microsomes

Mediates N- and S-oxidation reactions

Question 7

What co-factor is necessary for FMO?

Answer 7

NADPH

Question 8

What’re the two types of Monoamine oxidase - MAO? Where are they found?

Answer 8

MAO-A - found in liver, pulmonary vascular endothelial, GI tract and placenta

MAO-B - found in blood platelets

Both are found in neurons and astroglia

Question 9

What role does MAO play?

Answer 9

Had a vital role in the inactivation of endogenous neurotransmitters

Question 10

What compounds inhibit MAOs?

Answer 10

Antidepressants and caffeine

Question 11

What drug is metabolised by MAO?

Answer 11

Sumatriptan - used for treatment of migraine headaches

MAO-A converts tertiary amine to -COOH

Question 12

Where is aldehyde oxidase located?

Answer 12

Found in cytosolic compartment of tissues in many organisms

Question 13

What does aldehyde oxidase do?

Answer 13

Catalyses the oxidation of aldehydes into carboxylic acids

Catalyse the hydroxylation of some heterocycles

Can catalyse oxidation of both CYP450 and MAO intermediate products

Question 14

What does xanthine oxidase do?

Answer 14

Catalyses oxidation of hypoxanthine to xanthine and further oxidation to uric acid

Question 15

What does a build up of uric acid result in?

Answer 15

Gout

Question 16

What rare examples does xanthine oxidase catalyse?

Answer 16

XO is known to catalyse xenobiotic metabolism reactions

Question 17

Give an example of azo reduction

Answer 17

Prontosil is reduced to Sulphanilamide and an inactive by-product

Sulphanilamide is an active bacteriostatic

Question 18

What enzymes catalyse azo reduction?

Answer 18

Intestinal microbe reductases

Question 19

What enzymes catalyse nitro reduction?

Answer 19

Intestinal microflora nitroreductases

Question 20

What enzymes catalyses sulfoxide reduction?

Answer 20

Methionine sulfoxide reductase

Question 21

What enzyme catalyses the reduction of epoxides?

Answer 21

Epoxide reductase

Question 22

What enzyme catalyses the reduction of halogenated hydrocarbons?

Answer 22

Cytochrome P2E1

In presence of NADPH

Question 23

What’re the key hydrolysis enzymes?

Answer 23

Carboxylesterases

butyrylcholinesterases

Alkaline phosphatases

Paraoxanases

Epoxide hydrolase

Question 24

How is morphine activated?

Answer 24

Through dealkylation

Question 25

How is cocaine deactivated?

Answer 25

Through ester hydrolysis

Question 26

What enzyme catalyses lactone hydrolysis?

Answer 26

Paraxonases - activation of lovastatin, cholesterol lowering drug

Question 27

Where are Paraxonases synthesised and found?

Answer 27

Synthesised in liver —> transported to plasma

Question 28

Give an example of what alkaline phosphatase does.

Answer 28

Activation of Phenytoin, poorly water soluble, from Phosphentoin, water soluble.

Phosphoric acid is produced