Drug Metabolism CYP450 (DM14)

Question 1

What does xenobiotic metabolism target?

Answer 1

Environmental chemicals like Drugs or Polluants

Question 2

What does endobiotic metabolism target?

Answer 2

Cholesterol, steroids, bile acids, Vitamin D, fatty acids, retinoic acid, arachidonic acid

Question 3

What does the P in CYP450 mean?

Answer 3

Peak absorption at wave length 450. (CYP + CO complex absorbs light)

Question 4

What does 2 stand for in CYP2D6?

Answer 4

Gene family

Question 5

What does D stand for in CYP2D6?

Answer 5

Subfamily

Question 6

What does 6 stand for in CYP2D6?

Answer 6

Isoenzyme (structurally similar but different AA sequences)

Question 7

CYP450’s are proteins bound to what?

Answer 7

ER membrane

Question 8

What structure is a CYP450?

Answer 8

A prophyrin with Fe-Cysteine catalytic site

Question 9

Which family of CYPs has the most subfamilies and genes?

Answer 9

CYP2

Question 10

What are the Cytochrome P450 requirements/ingredients?

Answer 10

CYP450
CYP450 Reductase
NADPH (electron donor)
Molecular Oxygen (O2) Has to be O2 not just O

Question 11

What are the CYP450 reactions?

Answer 11

Aromatic hydroxylation
Aliphatic hydroxylation
Deamination
O-Dealkylation
N-Dealkylation
N-Oxidation
Sulfoxidation

Question 12

What are the clinically relevean CYP450s?

Answer 12

CYP1, CYP2, CYP3

Question 13

Which CYP450 isoform makes up 70% of the gut CYPs?

Answer 13

CYP3A

Question 14

What CYP450 isoforms metabolizes the most clinical drugs in order?

Answer 14

CYP3A4/5 (36%)
CYP2D6 (21%)
CYP2C8/9 (17%)

Question 15

What are the key isoforms for CYP related metabolism?

Answer 15

1A2, 2C19, 2C9, 2D6, 3A4,5,7

Question 16

What are the key isoform for CYP related inhibition?

Answer 16

1A2, 2B6, 2C9, 2D6, 3A4,5,7

Question 17

The CYP family metabolizes some drugs and carcinogens. T/F

Answer 17

True

Question 18

The CYP family does not exhibit inducibility & genetic polymorphism. T/F

Answer 18

False The CYP family DOES exhibit inducibility & genetic polymorphism.

Question 19

What do CYP1A1’s mostly metabolize?

Answer 19

Mostly environmental carcinogens and Inducible genetics.

Question 20

What do CYP1A2’s mostly metabolize?

Answer 20

Caffeine, Imipramine, Haloperidol, Fluvoxamine

Activates Aflatoxin B1

Question 21

The CYP2C9/2C19/2D6 metabolize how much of clinically important drugs?

Answer 21

25% includes warfarin, phenytoin, Mephenytoin, tolbutamide, glipzide

Question 22

Which CYPs are polymorphic and not induceable in humans?

Answer 22

CYP2C9 & 2C19 (poor metabolizers)

Question 23

The CYP2D6 is responsible for many DDI due to low expression. T/F

Answer 23

True

Question 24

What enzyme is mostly important for non-drugs such as ethanol, APAP toxicity, and halogenated Carbons?

Answer 24

CYP2E1

Question 25

Where is CYP3A7 found?

Answer 25

In deveoloping fetus

Question 26

Which CYP is largely responsible for the 1st pass effect?

Answer 26

CYP3A4/3A5

Question 27

What leads to differences in enzyme function?

Answer 27

Genetic variations

Question 28

If you have no CYP2D6 enzymes what occurs?

Answer 28

Too slow drug metabolism Too high drug levels at ordinary dosage High risk for Adverse reactions No response from certain prodrugs(codeine)

Question 29

If you have gene duplications of the CYP2D6 enzymes what occurs?

Answer 29

Too rapid drug metabolism | No drug response at ordinary dosage.

Question 30

What is tamoxifen for?

Answer 30

Used for cancer treatment

Question 31

Brain CYPs are inducible. T/F

Answer 31

True

Question 32

What are the consequences of altered activity of CYPs?

Answer 32

Drug efficacy | Neurotoxicity