nucleotide metabolism (20) Flashcards

1
Q

what are the 4 purines?

A

adeninin
guanine
hypoxanthine
xanthine

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2
Q

what are the 3 pyrimidines?

A

uracil
thymine
cytosine

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3
Q

list the 2 sources of ribose 5 phosphate

A
  • glucose metabolism, pentose phosphate shunt

- nucleoside degradation generates ribose-1-phosphate (which can be converted to R5P)

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4
Q

what two compounds are needed to synthesize PRPP? what is the enzyme?

A

ATP and ribose 5 phosphate

enzyme: PRPP synthase

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5
Q

list the 3 things that PRPP is required for

A
  1. De novo synthesis of pyrimidine & purine nucleotides
  2. The salvage pathways for purine nucleotides
  3. The biosynthesis of nucleotide coenzymes NAD and FAD
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6
Q

is this statement describing purines or pyramide synthesis?

the ring is built on a molecule of PPRP

A

purines

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7
Q

list the precursors for the purine ring

A

glutamine, glycine, CO2, aspartate and two 1 carbon fragments from the 1 carbon folate pool

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8
Q

how many high energy phosphate bonds are needed for the synethsis of IMP?

A

6

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9
Q

what step in IMP synthesis is considered the rate limiting and regulated step?

A

the 1st step

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10
Q

how many steps in IMP synthesis require folate?

A

2

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11
Q

how many steps in IMP synthesis can be blocked by azaserine?

A

2

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12
Q

what is azaserine an analog of?

A

glutamine

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13
Q

what does azaserine block?

A

the amide transfer from glutamine

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14
Q

what are sulfonamides an alalog of?

A

p-aminobenzoic acid

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15
Q

what do sulfonamides block?

A

the biosynthesisi of folic acid- so blocks nucleotide synthesis

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16
Q

how is de novo synthesis of purine nucleotides regulated?

A

feedback inhibition

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17
Q

what 3 compounds block the enzymes PRPP synthetase and PPRP amidotransferase? (enzymes that catalyze the 1st two steps of IMP synethsis)

A

IMP, GMP, AMP

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18
Q

what is the function of HGRT?

A

catalyzes the formation of nucleotides from either hypoxanthine or guanine. This enzyme is inhibited by IMP and GMP

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19
Q

what is the function of ARPT?

A

catalyzes the formation of AMP from adenine- inhibited by AMP

20
Q

is this statement describing purines or pyrimidines?

the ring is formed THEN it reacts with PRPP to form the nucleotide

A

pyrimidines

21
Q

what are the 2 precursors to the pyramidine ring?

A

carbamoylphosphate & asparate

22
Q

what do patients with OTC deficiencies build up high levels of pyrimidines in their serum & urine

A

because in OTC carbamoyl phosphate builds up and this is a precursor for the synthesis of pyramidines

23
Q

what is orotic aciduria?

A

genetic disorder of pyrmidine biosynthesis

24
Q

how can orotic aciduria be alleviated?

A

by feeding of uridine or cytidine→this supplies the body with the needed pyrimidine bases and inhibits CP II

25
Q

what is substrate channeling?

A

when 1 enzyme passes its product right off to the next to use as a substrate

26
Q

list the 6 enzymes that are inhibited by azaserine

A
  • CPSII
  • CTP synthase
  • FGAR aminotransferase
  • GMP synthase
  • PRPP aminotransferase
  • Aorargine synethase
27
Q

when are deoxynucleotides made?

A

during DNA replication

28
Q

what drug inhibits ribonucleotide reductase?

A

hydroxyurea

29
Q

what is the enzyme ribonucleotide reductase needed for?

A

in the formation of deoxynucleotides

30
Q

what reaction does thymidylate synthase catalyze? what form of THF is needed for this rxn?

A

dUMP–> dTMP

N5N10 methyleneTHF

31
Q

how is THF regenerated after the pathway that forms deoxyribonucleotides?

A

the enzyme dihydrofolate reductase which requires NADPH

32
Q

what drug inhibits dihydrofolate reductase? thereby inhibiting the regeneration of THF

A

methotrexate

33
Q

what is the function of 5-fluorouracil?

A

blocks the transfer of the methylene group to the pyrimidine ring

34
Q

what are the 2 ways that AMP can be degraded?

A
  1. Can first be deaminated to IMP→ then hydrolyzed to inosine
  2. Or can be hydrolyzed to adenosine then demaminated to inosine
35
Q

how is GMP degraded?

A

it is hydrolyzed to guanosine

36
Q

how is CMP degraded?

A

can be deaminated to UMP and then hydrolyzed to uridine-or it can be hydrolyzed to cytidine and then deaminated the uridine

37
Q

what is the final product of purine degradation?

A

uric acid

38
Q

what is the enzyme xanthine oxidase

A
enzyme required for breakdown of AMP and the oxidation to uric acid
contains molybdenum  (only known function in the human body of this element)
39
Q

what is the final product of pyrimidine degradation?

A

uracil: B-alanine
thymine: B- aminoisobutyrate

40
Q

what is the cause of gout?

A

caused by precipitation of sodium urate crystals in the joints & kidneys

41
Q

what are the 2 circumstances that can cause gout?

A
  1. abnormal PRPP synthetase and not responsive to feedback inhibition
  2. HGPRT deficiency leads to increased PRPP levels (so greater de novo synthesis of purines)
42
Q

what is the treatment for gout?

A

allopurinol (which blocks the production of uric acid)

43
Q

what is lesch nyhan syndrome?

A

X linked recessive condition due to severe or complete deficiency of HGPRT

44
Q

what are the symptoms of lesch nyhan syndrome?

A

Hyperuricemia, gout, urinary tract stones and neurological symptoms (mental retardation, spasticity and self mutilation)

45
Q

what is the treatment for lesch nyhan sydrome?

A

can use allopurinol to reduce the uric acid formation but it does NOT alleviate the neuro symptoms
Can also be treated with: low protein diet, cochicine and a low purine diet

46
Q

what is the cause of adenosine deaminase deficiency?

A

deoxyadenosine & adenosine are abundant and are not degraded but are efficiently converted to nucleotides in white blood cells
High levels of dATP inhibit ribonucleotide reductase which inhibits DNA synethsis- so the WBCs

47
Q

what is the treatment for adensoine deaminase deficiency?

A

bone marrow transplantation & enzyme replacement therapy

Gene therapy has been experimented