Purine and pyrimidine synthesis Flashcards Preview

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Flashcards in Purine and pyrimidine synthesis Deck (36):
1

Which substrate in pyrimidine synthesis would be lowered due to 5-FU treatment?

dTMP

 

(Inhibitis thymidylate synthase = dUMP  --->  dTMP)

1

What is required for de novo purine synthesis?

Aspartate, glutamine, glycine, THF

2

Cofactor?

Orotic acid  --->  UMP

PRPP

2

MOA of hydroxyurea?

Ribonucleotide reductase

 

(Inhibits UDP -->  dUDP)

2

Which substrate in purine synthesis would be lowered as a result of treatment with ribavirin or mycophenolate?

GMP

 

(Inhibit IMP dehydrogenase, so inhibit IMP  --->  GMP)

3

Which substrate in pyrimidine synthesis would be higher with TMP, pyrimethamine, or MTX treatment? Lower?

dUMP higher

dTMP lower

 

(Inhibits DHFR = needed for reduction of DHF to THF to regenerate N5N10-methylene THF, the cofactor for  dUMP  --->  dTMP reaction)

4

Enzyme?

UDP  --->  dUDP

Ribonucleotide reductase

6

Enzyme?

dUMP  -->  dTMP

Thymidylate synthase

7

Which enzyme activates 6-MP?

HGPRT

8

Which substrate in purine synthesis would be lower as a result of treatment with 6-mercaptopurine?

IMP

 

(Inhibits PRPP  --->  IMP)

8

Which drug inhibits pyrimidine synthesis is bacteria specifically? Protozoa specifically?

Trimethoprim

Pyrimethamine

 

(DHFR inhibitors)

9

MOA leflunomide?

Inhibits dihydroorate dehydrognase

 

(Inhibits carbamoyl phosphate  --->  orotic acid)

10

Which drug would cause higher levels of PRPP?

6-mercaptopurine

 

(Inhibits PRPP  --->  IMP)

11

Elevated DHF levels are indicative of treatment with which drugs?

Trimethoprim

Methotrexate

Pryrimethamine

13

Steps in pyrimidine synthesis

Glutamine + CO2 ---> Carbamoyl phosphate ---> Orotic acid ---> UMP ---> UDP ---> CTP + dUDP ---> dUMP ---> dTMP

13

Which step in purine synthesis is inhibited by 6-mercaptopurine?

PRPP  --->  IMP

15

Which step in pyrimidine synthesis is impaired in orotic aciduria?

Orotic acid  --->  UMP

16

Which enzyme is needed for degradation of 6-MP?

TPMT and xanthine oxidase

 

(activated by HGPRT)

17

Enzyme?

Ribose-5-P  --->   PRPP

PRPP synthetase

19

Which drug would results in high levels of UDP?

Hydroxyurea

 

(Inhibits ribonucleotide reductase, so inhibits UDP  --->  dUDP)

19

Enzyme?

DHF  --->  THF

Dihydrofolate reductase

20

Which substrate in pyrimidine synthesis would be lowered as a result of hydroxyurea treatment?

dUDP

 

(Inhibits ribonucleotide reductase, so inhibits UDP  --->  dUDP)

21

Which drugs would cause higher levels of IMP?

Ribavirin, mycophenolate

 

(Inhibit IMP dehydrogenase, so inhibits IMP  --->  GMP)

23

Which two pathways utilize carbamoyl phosphate?

De novo pyrimidine synthesis and urea cycle

24

Cofactor?

dUMP  --->  dTMP

N5N10- methylene THF

 

(DHF is product of this reaction, needs to be reduced back to THF)

25

Which substrate of pyrimidine synthesis is also involved in urea cycle?

Carbamoyl phosphate

27

Which drug inhibits thymidylate synthase?

5-FU

 

(Inhibits dUMP  --->  dTMP)

28

Steps in purine synthesis

Ribose-5-P ---> PRPP ---> IMP ----> AMP + GMP

29

MOA mycophenolate and ribavirin

Inhibit IMP dehydrogenase

 

(Inhibit IMP  --->  GMP)

30

Enzyme?

Carbamoyl phosphate  --->  Orotic acid

Dihydroorotic acid dehydrogenase

31

Which drug would result in increased levels of dUMP?

5-FU

 

(Inhibits thymidylate synthase, so inhibits dUMP  --->  dTMP)

32

Would THF levels be increased or reduced due to treatment with MTX, TMP, or pyrimethamine?

Reduced

 

(Inhibits dihydrofolate reductase =  DHF  --->  THF)

33

Enzyme?

Glutamine + CO2  --->  Carbamoyl phosphate

Carbamoyl phosphate synthetase II

34

Which drug inhibits dihydroorate dehydrogenase?

Leflunomide

35

Which two cofactors are needed for both de novo purine and de novo pyrimidine synthesis?

THF, aspartate

36

Cofactor?

Carbamoyl phosphate  --->  Orotic acid

Aspartate