Lecture 30: nucleotide metabolism Flashcards

1
Q

What is the important precursor for all nucleotides?

A

PRPP

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2
Q

pyrimidines for nitrogenous bases _____ of PRPP

A

independent

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3
Q

Do pyrimidines do unidirectional or branched pathway?1

A

unidirectional

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4
Q

pyrimidine precursors used

A

NH3 from Gln
Asp
HCO3-

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5
Q

how is allosteric regulation used in de novo synthesis of ribonucleotides?

A
pyrimidines inhibit (C) 
purines activates (A/G)
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6
Q

What is CAD?

A

multifunctional, eukaryotic protein performs the functions of:
carbamoyl phosphate synthetase II (CPSII)
aspartate transcarbamoylase (ATCase)
dihydroorotase

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7
Q

Does carbamoyl phosphate synthetase II have a channel?

A

yes

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8
Q

What are the two allosteric regulators of aspartate transcarbamoylase?

A

ATP activates

CTP inhibits

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9
Q

what does dihydroorotase do?

A

closes the ring (hydrolase in reverse)

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10
Q

where is dihydroorotase dehydrogenase located?

A

in mitochondria

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11
Q

What is UMP synthetase?

A

multifunctional, eukaryotic protein
removes PPi when rotate added to PPRP
decarboxylates rotate to form uracil

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12
Q

When does megaloblastic anemia occur?

A

when cells fail to divide

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13
Q

What are the most common causes of megaloblastic anemia?

A

B9 and/or B12 deficiencies

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14
Q

What are the symptoms of hereditary orotic aciduria? what causes it?

A

symptoms: excessive rotate excreted in urine, megaloblastic anemia that fails to respond to B9/B12 treatment
caused by deficiency of UMP synthetase

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15
Q

____ is the only nucleotide to be synthesized directly as a triphosphate

A

CTP

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16
Q

What are the two allosteric regulators of CTP synthetase?

A

GTP activates and CTP inhibits

17
Q

Purines form a nitrogenous base ____ PRPP

A

on

18
Q

Do purines use a branched or unidirectional pathway?

A

branched

19
Q

What are the precursors for purines?

A

NH3 from Gln
Gly, Asp
N10-formyl-THF
HCO3

20
Q

What occurs in reactions 1-3 when making IMP from purines?

A
forming 5 membered ring 
1. swaps PPi on PRPP for NH3 from Gln
2. adds glycine
3. adds formyl group from N10 formyl THF to complete the ring
LOOK AT SLIDES
21
Q

What occurs in reactions 4-10 when making IMP from purines?

A

forming 6 membered ring

  1. adds NH3 from Gln to start the second ring
  2. closes the 5 membered ring
  3. adds CO2 from HCO3 first to Gln then to Gly
  4. adds Asp at the carboxyl
  5. releases fumarate
  6. second addition of a formyl group from another N10 formyl THF, completing the 6 membered ring
  7. closes the 6 membered ring, forming hypoxanthine
22
Q

When purines branch off of IMP, what does AMP do?

A

uses GTP for energy
replaces Carbonyl with NH3 from Asp
releases fumarate
inhibited by AMP

23
Q

When purines branch off of IMP, what does GMP do?

A

uses ATP for energy
redox H20 to make second carbonyl
replaces it with NH3 from Gln
inhibited by GMP

24
Q

____ provides the necessary electrons for redox reactions

A

NADPH

25
Q

ribonucleotide reductase makes ____

A

dNDPs

26
Q

What promotes the function of ribonucleotide reductase? turns off?

A

promotes : ATP

turns off: dATP by altering subunit contacts

27
Q

dATP active site

A

pyrimidines preferred

28
Q

dTTP active site

A

GDP preferred, pyrimidines inhibited

29
Q

dGTP active site

A

ADP preferred, pyrimidines inhibited

30
Q

What are the two ways to create dUMP?

A

removal of PPi from dUTP

deamination of dCMP

31
Q

_____ adds a methyl to dUMP to create dTMP

A

thymidylate synthase

32
Q

endonuclease do what?

A

cut in the middle

33
Q

exonuclease do what?

A

chew from the end

34
Q

phosphorylates make ____

A

nucleosides

35
Q

kinases make ____

A

nucleotides

36
Q

What is the final step in purine catabolism?

A

uric acid

37
Q

What is Gout? and symptoms

A

chronic elevated levels of irate in the blood (hyperuricemia) results in uric acid crystals collecting in joints.
symptoms: inflammation
arthritis
joint degeneration

38
Q

What is a pathology that can produce gout?

A

HPRT deficiency (Lesch-Nyhan syndrome)

39
Q

What is severe combined immunodeficiency disease (SCID) a deficiency of?

A

adenosine deaminase