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Step One R&M > Purine and pyrimidine synthesis > Flashcards

Purine and pyrimidine synthesis Flashcards

1
Q

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

A

dTMP

(Inhibitis thymidylate synthase = dUMP —> dTMP)

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1
Q

What is required for de novo purine synthesis?

A

Aspartate, glutamine, glycine, THF

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2
Q

Cofactor?

Orotic acid —> UMP

A

PRPP

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2
Q

MOA of hydroxyurea?

A

Ribonucleotide reductase

(Inhibits UDP –> dUDP)

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2
Q

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

A

GMP

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

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3
Q

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

A

dUMP higher

dTMP lower

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

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4
Q

Enzyme?

UDP —> dUDP

A

Ribonucleotide reductase

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6
Q

Enzyme?

dUMP –> dTMP

A

Thymidylate synthase

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7
Q

Which enzyme activates 6-MP?

A

HGPRT

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8
Q

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

A

IMP

(Inhibits PRPP —> IMP)

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8
Q

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

A

Trimethoprim

Pyrimethamine

(DHFR inhibitors)

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9
Q

MOA leflunomide?

A

Inhibits dihydroorate dehydrognase

(Inhibits carbamoyl phosphate —> orotic acid)

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10
Q

Which drug would cause higher levels of PRPP?

A

6-mercaptopurine

(Inhibits PRPP —> IMP)

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11
Q

Elevated DHF levels are indicative of treatment with which drugs?

A

Trimethoprim

Methotrexate

Pryrimethamine

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13
Q

Steps in pyrimidine synthesis

A

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

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13
Q

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

A

PRPP —> IMP

15
Q

Which step in pyrimidine synthesis is impaired in orotic aciduria?

A

Orotic acid —> UMP

16
Q

Which enzyme is needed for degradation of 6-MP?

A

TPMT and xanthine oxidase

(activated by HGPRT)

17
Q

Enzyme?

Ribose-5-P —> PRPP

A

PRPP synthetase

19
Q

Which drug would results in high levels of UDP?

A

Hydroxyurea

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

19
Q

Enzyme?

DHF —> THF

A

Dihydrofolate reductase

20
Q

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

A

dUDP

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

21
Q

Which drugs would cause higher levels of IMP?

A

Ribavirin, mycophenolate

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

23
Q

Which two pathways utilize carbamoyl phosphate?

A

De novo pyrimidine synthesis and urea cycle

24
Q

Cofactor?

dUMP —> dTMP

A

N5N10- methylene THF

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

25
Q

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

A

Carbamoyl phosphate

27
Q

Which drug inhibits thymidylate synthase?

A

5-FU

(Inhibits dUMP —> dTMP)

28
Q

Steps in purine synthesis

A

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

29
Q

MOA mycophenolate and ribavirin

A

Inhibit IMP dehydrogenase

(Inhibit IMP —> GMP)

30
Q

Enzyme?

Carbamoyl phosphate —> Orotic acid

A

Dihydroorotic acid dehydrogenase

31
Q

Which drug would result in increased levels of dUMP?

A

5-FU

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

32
Q

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

A

Reduced

(Inhibits dihydrofolate reductase = DHF —> THF)

33
Q

Enzyme?

Glutamine + CO2 —> Carbamoyl phosphate

A

Carbamoyl phosphate synthetase II

34
Q

Which drug inhibits dihydroorate dehydrogenase?

A

Leflunomide

35
Q

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

A

THF, aspartate

36
Q

Cofactor?

Carbamoyl phosphate —> Orotic acid

A

Aspartate

Step One R&M (38 decks)

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