Cytochrome p450 enzymes and drug metabolism 1

Question 1

Name the 2 phases of metabolism

Answer 1

Phase 1 and 2

Question 1

Define phase 1 metabolism

Answer 1

Functionalisation/ activation of drugs (Often oxidative)
Performed by CYP 450 enzymes

Question 2

Define phase 2 metabolism and name the 2 enzymes involved in phase 2 metabolism

Answer 2

Enzyme families involved in conjugation for detoxification and/or excretion

UDP-glucuronic acid transferases (UDPGTs) and glutathione-S-transferases

Question 3

What is xanthine oxidase involved in?

Answer 3

Metabolism of DNA/ RNA bases
Oxidation reaction - hydroxylation and tautomerisation - amide formed

Question 4

Name the drugs that xanthine oxidase metabolises

Answer 4

Theophylline, theobromine and caffeine

Question 5

Name the phase 1 reactions

Answer 5

Oxidations
Hydrolysis
Hydration
Dethioacetylation
Isomerisation
Reduction

Question 6

Describe CYP 450 enzymes

Answer 6

found in the liver
many found in the ER
Reaction requires NADPH, O2 NADPH-cytochrome p450 reductase - used by an auxiliary enzyme
are inducible - increased expression by small molecules/drugs - results in faster metabolism of all drugs processed by the same enzyme

Question 7

What is the most common type of reaction used by CYP 450 enzymes?

Answer 7

Hydroxylation - mist common type of oxidative reaction catalysed by these types of enzymes
Reactions are usually stereoselective - one isomer. often metabolised
Reactions are regiospecific

Question 8

Whats important about chiral drugs?

Answer 8

Often metabolised to different products with different kinetics and rates of drug metabolism
Different stereoisomers of drugs are different drugs

Question 9

Describe the mechanism of cytochrome p450 enzymes

Answer 9

Enzyme possess a haem group
Reaction requires dioxygen, NADPH and an auxiliary enzyme
Enzymes catalyse their reactions via negative catalysis

Question 10

Define superfamily

Answer 10

The whole group of enzymes that catalyse the same or a similar type of reaction using a similar mechanism and are related by primary sequence homology or identity

Question 11

Name the 3 different subfamilies involved in drug metabolism

Answer 11

CYP enzymes
UDP-glucuronosyl transferases (glucuronidation)
Glutathione-S-transferases (glutathione conjugation)

Question 12

Define homology

Answer 12

sequences are aligned an amino acid in a particular position is conserved by type e.g. leucine could be substituted for a isoleucine or valine

Question 13

Define identity

Answer 13

when sequences are aligned an amino acid in a particular position is always the same i.e. leucine must be a leucine

Question 14

Name the important members of the super family for drug metabolism

Answer 14

CYP3A4,A5,A7, 2D6, 2E1

Question 15

Define uncoupled reaction cycles

Answer 15

Dioxygen, and NADPH are consumed but substrate is not oxidised
Product is reduced oxygen (hydrogen peroxide)