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UWorld Review > purine/pyrimidine metabolism > Flashcards

purine/pyrimidine metabolism Flashcards

1
Q

Drugs affecting pyrimidine synthesis

A

Leflunomide MTX, TMP, pyrimethanine 5-FU/capecitabine (prodrug)

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2
Q

Drugs affecting purine synthesis

A

6-MP, azathioprine (prodrug) mycophenolate and ribavirin

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3
Q

Drug that affects both pyrimidine/purine synthesis

A

Hydroxyurea inhibits ribonucleotide reductase (UDP to dUDP) build up of UDP

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4
Q

inhibits dihydroorotate dehydrogenase

A

leflunomide no orotic acid (carbamoyl phosphate + aspartate) inhibit pyrimidine

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5
Q

inhibits dihydrofolate reductase decrease deoxythymidine monophosphate (dTMP) in humans, bacteria, protozoa

A

MTX, TMP, pyrimethamine (inhibit pyrimidine) get build up of DHF

  • MTX=eukaryotes
  • TMP=prokaryotes
  • pyrimethamine=protozoa
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6
Q
  • form 5-FdUMP
  • inhibits thymidylate synthase decrease dTMP increase dUMP
A

5-FU and its prodrug capecitabine inhibit pyrimidine

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7
Q

inhibit de novo purine synthesis

A

6-MP and azathioprine (prodrug) no IMP made build up of PRPP

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8
Q

inhibit inosine monophosphate dehydrogenase

A

mycophenolate ribavirin build up of IMP can’t make GMP (inhibit purine)

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9
Q

pyrimidine base production requires

A

aspartate

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10
Q

de novo purine synthesis requires

A

aspartate glycine glutamine THF

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11
Q

Start of pyrimidine synthesis

A

glutamine + CO2 + 2 ATP Carbamoyl phosphate synthetase II (CPS2) in cyTWOsol

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12
Q

Start of purine synthesis

A

Ribose-5-P –> PRPP –> IMP

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13
Q

In orotic acuduria, cannot make

A

UMP from orotic acid and PRPP

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14
Q

one of major causes of AR SCID

A

adenosine deaminase deficiency

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15
Q

adenosine deaminase is required for

A

degradation of adenosine and deoxyadenosine decrease ADA cannot make inosine from adenosine increase dATP increase lymphotoxicity = AR SCID

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16
Q

Disease with defective purine salvage d/t to absent HGPRT

A

Lesch-Nyhan syndrome XR

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17
Q

HGPRT converts

A

hypoxanthine to IMP guanine to GMP

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18
Q

what consequences come from absent HGPRT (Lesch-Nyhan syndrome, XR)

A

excess uric acid production and de novo purine synthesis

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19
Q

presentation of Lesch-Nyhan

A

XR -intellectual disability -self-mutiliation -aggression -hyperuricemia, orange “sand” [sodium rate crystals] in diaper -gout -dystonia

20
Q

How to treat Lesch-Nyhan

A

allopurinol febuxostat (2nd line) inhibit XO decrease uric acid levels

21
Q

How to Dx Lesch-Nyhan

A

increase uric acid in urine ID gene mutation

22
Q

Uric acid –> urine is done by

A

Rasburicase

23
Q

What drug increases uric acid –> urine

A

Probenicid used in gout

24
Q

What drug inhibits uric acid –> urine

A

Aspirin

25
Q

Hypoxanthine –> Xanthine Xanthine –> Uric acid done by

A

xanthine oxidase both inhibited by allopurinol and febuxostat

26
Q

What purine is this

A

Adenosine

amino group at 12’o clock

27
Q

What purine is this

A

Guanine

28
Q

What is this molecule when 7 o’ clock amino group is missing

A

hypoxanthine

29
Q

Pyrimidine with 12 o’ clock amino group

A

cytosine

30
Q

pyrimidine with no 12 o ‘ clock amino group

A

uracil

31
Q

pyrimidine with 1 o’ clock methyl group added to uracil

A

thymine

32
Q

Ribose for purine/pyrimidine synthesis made from

A

HMP shunt

33
Q

What cells have CPS2

A

cytosol of all cells EXCEPT erythrocytes

34
Q

CPS1 is located where

A

mitochondria

(urea cycle)

35
Q

carbamoyl phosphate is made in what two places

A

cytosol - de novo pyrimidine synthesis by CPS II

mitochondria - urea cycle by CPS I

36
Q

what to know about orotic acid

A

it is a pyrimidine precursor

37
Q

What does thymidylate synthase do

A

adds methyl group from N5N10 methylene THF to dUMP to make dTMP

38
Q

What does dihydrofolate reductase do

A

reduces DHF and adds methyl group (from serine/glycine) to make THF

39
Q

What is a big consequence of OTC deficiency from urea cycle

A
  • increase of carbamoyl phosphate in mitochondria that leaks into cytosol
  • carbamoyl phosphate (from mito) can be turned into pyrimidine w/CPS II
  • increase in orotic acid, seen in urine
40
Q

Increase of orotic acid in urine is a sign of

A

OTC deficiency from urea cycle

or

defective pyrimidine synthesis of orotic acid to UMP

41
Q

How to distinguish where orotic aciduria is coming from in a kid

A
  • if urea cycle problem w/OTC deficiency = elevated ammonia/hyperammonemia, decreased BUN
  • If BUN normal, must be orotic aciduria from pyrimidine synthesis
42
Q

what is the first step of purine synthesis

A
  • PRPP –> 5-Phosphoribosylamine
  • via PRPP amidotransferase
43
Q

IMP can make (purine synthesis)

A
  • GMP after getting amino group from glutamate
  • AMP after getting amino group from aspartate
44
Q

IMP, GMP, and AMP are

A

nucleotides

base, (deoxy)ribose, and phosphate

45
Q

What inhibits PRPP amidotransferase

A

IMP, AMP, GMP

46
Q
A

UWorld Review (35 decks)

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