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Biochem -Exam 3 > Drugs and Diseases: Purine, Pyrimidine metabolism > Flashcards

Drugs and Diseases: Purine, Pyrimidine metabolism Flashcards

1
Q

derivatives of purine C’s and N’s

A 
N1: Asp amino 
C2, C8: C1-THF 
N3, N9: Gln amide 
C6: HCO3-
C4, C5, N7: Gly
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2
Q

what causes Lesch-Nyhan syndrome?

A

HGPRT deficiency

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3
Q

how is Lesch-Nyhan inherited?

A

x-linked

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4
Q

symptoms of Lesch-Nyhan?

A
  • increased uric acid, xanthine
  • increased purine synthesis to compensate
  • neuro disease: athetosis, chorea, dystonia, self mutilation
  • urate nephrolithiasis
  • hyperuricemia
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5
Q

how do you treat Lesch-Nyhan?

A

allopurinol - competitive inhibitor of xanthine oxidase (suicide inhibitor)

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6
Q

what causes gout?

A

high serum uric acid

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7
Q

symptoms of gout

A

-tophus lesion (deposit of uric acid crystals + inflam) in extremities, at night (temp related)

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8
Q

3 known metabolic causes of gout

A
  1. increased PRPP synthetase activity
  2. HGPRT deficiency
  3. G-6-phosphatase deficiency (von Gierke’s) - indirect
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9
Q

treatment of gout

A
  • allopurinol (lower uric acid)
  • colchicine (no neutrophil migration)
  • decreased alcohol (increase lactate = lower pH = decreased uric acid solubility)
  • NSAIDS (no excretion of urate)
  • uricase (urate -> allantoin)
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10
Q

what is correlated with gout attacks?

A

fructose

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11
Q

what causes SCID?

A

ADA (adenosine deaminase deficiency)

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12
Q

symptoms of SCID

A
  • no B or T cells
  • recurrent infections
  • increased dATP in lymphocytes -> decreased ribonucleotide reductase -> less trans-methylation
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13
Q

what does purine nucleoside phosphorylase deficiency cause?

A
  • no T cell fxn
  • accumulation of inosines, guanosines
  • recurrent infections
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14
Q

what are two targets for chemo? which chemos target each?

A
  1. thymidylate synthase - fluorodeoxyuridylate (suicide inhibitor)
  2. DHFR - aminopterin and MTX (amethopterin)
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15
Q

2 antiviral agents that are purine analogs?

A
  1. acyclovir (acycloguanosine)

2. ganciclovir

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16
Q

what activates acyclovir and ganciclovir?

A

activated to mono-phosphate by viral HSV-thymidine kinase

17
Q

mechanism of action of acyclovir and ganciclovir?

A

tri-phosphate is substrate for HSV-specific DNA pol -> causes DNA chain termination of viral gene products

18
Q

what is ganciclovir used to treat?

A

cytomegalovirus infections in HIV patients

19
Q

2 antiviral agents that are pyrimidine analogs?

A
  1. AZT (azido-d’-deoxythymidine)

2. DDI (2’,3’-dideoxyinosine)

20
Q

activation of AZT?

A

phosphorylated by cellular kinases

21
Q

action of AZT?

A

blocks HIV replication - inhibits HIV-DNA pol, which is RNA-dependent

22
Q

action of DDI?

A

chain termination mechanism

23
Q

what is an antiviral agent used to treat HepB?

A

FIAU (fialuridine/ 1-(2-deoxy-2-fluro-arabinosyl)-5-iodouracil)

  • added into mito DNA via DNA pol gamma -> no mito division
  • lactic acidosis from increased anaerobic glycolysis

caused liver failure in one patient

24
Q

what is used to estimate DNA turnover?

A

beta-aminoisobutyrate (increased in chemo/rad patients)

25
Q

name 4 chemo agents?

A
  1. 5-fluorouracil/ FUra/ 5-FU
  2. AraC (cytosine arabinoside)
  3. MTX (methotrexate)
  4. hydroxyurea
26
Q

what is 5-fluorouracil and what is it used to treat?

A
  • uracil analog
  • treat solid tumors (ovary, cervix, prostate, colorectal)
  • inhibits precursor rRNA from dividing (5’ tri-P inserted in RNA)
  • inhibits thymidylate synthase -> DNA breaks
27
Q

what is AraC and what is it used to treat?

A
  • antileukemic

- inhibits DNA synthesis (5’ tri-P inserted into DNA)

28
Q

what is MTX and what is it used to treat?

A
  • inhibits DHFR (inhibits THF formation)

- treats human cancer (leukemia)

29
Q

what rescues normal cells in leukemia treatment w/ MTX?

A

leucovorin

30
Q

what is hydroxyurea and what does it treat?

A
  • inhibits DNA synthesis but not RNA/protein synthesis
  • acts on ribonucleotide reductase
  • limited clinically (rapid clearance, need [high])

Biochem -Exam 3 (9 decks)

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