Biotransformations

Question 1

What gives a substrate a better chance for excretion?

Answer 1

the formation of a more polar metabolite

goal is to go from lipid soluble → water soluble

Question 2

What is the cytochrome P450 system composed of?

Answer 2

flavoprotein

lipid (membrane- SER)

hemoprotein

Question 3

Flavoprotein

Answer 3

NADPH - P450 oxidoreductase

Question 4

Lipid

Answer 4

phosphatidyl choline

Question 5

Hemoprotein

Answer 5

cytochrome b₅

cytochrome P450

Question 6

What is the reductase- P450 ratio?

Answer 6

1:10 → 1:100

Question 7

How many cytochrome P450 gene families are there in mammals?

Answer 7

8

Question 8

How many cytochrome P450 gene families are there in drug metabolism? What are they?

Answer 8

4

CYP1, CYP2, CYP3, CYP4

Question 9

Where is the cytochrome P450 gene family expressed?

Answer 9

liver, lungs, intestines, skin and kidney

Question 10

What is the flavoprotein function in the P450 system?

Answer 10

to reduce the system with NADPH

Question 11

What is induction dependent on?

Answer 11

ability of intracellular receptors

Question 12

How many genes are present of CYP 1?

Answer 12

2

with 100 fold inducibility

Question 13

What are the inducers of CYP1?

Answer 13

1. metilcholantrene
2. dioxin derivatives
   
   • ​​industrial technologies
   • environmental pollution
3. Cigarette smoke

Question 14

What can be a consequence of inducibility of CYP 1 ?

Answer 14

incidence of bronchial carcinoma

Question 15

What are the substrates of CYP 1?

Answer 15

1. Policyclic aromatic hydrocarbons (PAH)
   
   • benzpyrene, benzanthracene
2. Medicines
   
   • teophyllin, caffeine, phacetin

Question 16

What is TEXB? for CYP 1

Answer 16

total effective xenogenic burden

endocrine disrupters

Question 17

What is the intracellular receptor/transcription factor responsible for induction?

Answer 17

Ah

(aryl hydrocarbon receptor)

Question 18

What are the inducers of CYP2?

Answer 18

phenobarbital

ethanol

acetone

diazepam derivatives

Question 19

What is the intracellular receptor/ transcription factor responsible for induction of CYP 2?

Answer 19

CAR

phenobarbital

Question 20

CYP 2A

Answer 20

steroids

testosterone

Question 21

CYP 2B

Answer 21

progesterone

D₃ vitamin

antiepileptics

Question 22

CYP 2C

Answer 22

mephenytoin - antiepileptics

Question 23

CYP 2D

Answer 23

antidepressants

beta blockers

antihypertensive agents

Question 24

CYP 2E

Answer 24

ethanol, acetone

• diabetes meelitus, starvation

Question 25

What are the **inducers** of **CYP 3**?

Answer 25

steroids * oral contraceptives * PCN- pregnenolon carbonitril

Question 26

What are the **substrates** of **CYP 3**?

Answer 26

antibiotics nifedipin cyclosporin

Question 27

What are the endocrine disrupters for CYP3?

Answer 27

total effective **xenosestrogenic** burden TEXB

Question 28

What are the **inducers** of **CYP 4**?

Answer 28

clofibrate -antihyperlipemic agent

Question 29

What are the **substrates** of **CYP 4**?

Answer 29

fatty acids eicosanoids

Question 30

What are the **substrates** of **CYP 4**?

Answer 30

fatty acids eicosanoids

Question 31

What is the intracellular receptor/ transcription factor responsible for induction of **CYP 4** ​?

Answer 31

PPAR

Question 32

What are the nuclear receptors in regulation of drug metabolism ?

Answer 32

CAR LXR PXR PPARαβγ

Question 33

CAR

Answer 33

androstanes phenobarbital

Question 34

LXR

Answer 34

oxysterols

Question 35

PXR

Answer 35

pregnanes

Question 36

PPARαβγ

Answer 36

fatty acids eicosanoids

Question 37

What is a "gene battery" ?

Answer 37

biotransformation phase I, II enzymes ABC transporters phase III + metabolic regulations

Question 38

What are the possible processes of conjugation?

Answer 38

1. glucuronidation 2. sulfation 3. GSH conjugation 4. Acetylation 5. Amino acid conjugation 6. Methylation

Question 39

What are frequent UGT substrates?

Answer 39

**I.** gene family isoenzymes: fenols,bilirubin **II.** gene family isoenzymes: steroids, bile acids

Question 40

What is the **activation** of the UGT substrates?

Answer 40

morphine, steroids, bile acids, retinoids, polycyclic aryl hydrocarbones, heterocycle aryl amines

Question 41

What is the rold of UGT-s in activation of drugs?

Answer 41

* morphin * steroids * bile acids * retinoids →polycyclic aromatic hydrocarbons →heterocyclic aromatic amines

Question 42

What are examples of unconjugated hyperbilirubinemias?

Answer 42

Gilbert disease Crigler - Najjar syndrome

Question 43

What is Gilbert disease?

Answer 43

* SNP-s in promoter region of UGT genes * **Low** **UGT activity** * benign, 5-6% of population

Question 44

What is the treatment for Gilberts disease?

Answer 44

inducer- **phenobarbital**

Question 45

What is the problem in **Crigler- Najjar Syndrome**?

Answer 45

**early stop codon in UGT genes** bilirubin enecephalopathia, fatal

Question 46

What are the **conjugated** hyperbilirubinemias?

Answer 46

Dubin Johnson syndrome Rotor Syndrome

Question 47

What are the problems in Dubin Johnson and Rotor Syndrome?

Answer 47

transport of conjugates is disturbed **expression of MRP2** is depressed

Question 48

What is the method of conjugation by **glucuronidation**?

Answer 48

UDP glucuronate Enzyme: UDP glucuronosyl transferase (UGT)

Question 49

What is the method of conjugation by sulfation

Answer 49

PAPS Enzyme: sulfotransferases

Question 50

What is the method of conjugation by GSH ?

Answer 50

GSH, acetyl CoA Enzyme: GSH transferases

Question 51

What is the method of conjugation by **acetylation**?

Answer 51

acetyl CoA

Question 52

What is the method of conjugation by **Amino acid conjugation**?

Answer 52

amino acids

Question 53

What is the method of conjugation by **methylation**?

Answer 53

SAM

Question 54

What are the intracellular cofactors of toxicity? (what lol)

Answer 54

NADPH UDPGA PAPS GSH vitamins