Exam 3 Nucleotide Metabolism (DNA) Flashcards

1
Q

dNTPs synthesis overview:

A

take any rNDP, reduce it (ie removed -OH) to make dNDPs then add phosphate to made dNTPs

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2
Q

what is the enzyme that will reduce ribose into deoxyribose

A

ribonucleotide reductase

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3
Q

how does ribonucleotide reductase perform redox rxn

A

creates free radicals eg catalytic Tyr free radical

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4
Q

why is ribonucleotide reductase not picky

A

this one enzyme acts on all NDPs and can act on NTPs

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5
Q

NADPH provides

A

the necessary e-s for redox rxns

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6
Q

ribonucleotide reductase makes

A

dNDPs

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7
Q

how many regulation sites are on ribonucleotide reductase

A

3; 1 catalytic site and 2 allosteric sites

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8
Q

what promotes function in allosteric site in ribonucleotide reductase

A

ATP

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9
Q

what turns off function in allosteric site in ribonucleotide reductase

A

dATP

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10
Q

the allosteric site preference for activity is called what in ribonucleotide reductase

A

specificity site; it is a volume dial ie regulates exact amount of activity

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11
Q

what do kinases do in deoxyribonucleotide synthesis

A

all the dNDPs are converted to dNTPs

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12
Q

why is dTTP special

A

it makes a detour in making dTTP from UDP

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13
Q

what are the ways to make dUMP for dTTP synthesis

A
  1. remove PPi (pyrophosphate) from dUTP

2. deamination of dCMP

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14
Q

to make T (thymine) in deoxy, need extra _ group

A

methyl

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15
Q

what adds a methyl to dUMP to create dTMP

A

thymidylate synthase

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16
Q

what is the methyl donor in dTMP synthesis

A

B9/methyl-THF

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17
Q

what is the clinical relevance of 5-FU?

A

it makes an unusable substrate for thymidylate synthase (it is a suicide inhibitor) which stops T pathway synthesis

18
Q

how do we regenerate THF?

A

NADPH used for reduction of dihydrofolate (DHF)

19
Q

what do the two drugs that competitively inhibits dihydrofolate reductase accomplish? drug names are methotrexate and trimethoprim

A

inhibit ability to incorporate T in DNA (good for cancer)

20
Q

how does endonucleases work

A

“inside” cut in the middle

21
Q

how does exonucleases work

A

“outside” chew from the end

22
Q

endonucleases make

A

oligonucleotides

23
Q

exonucleases make

A

nucleoside monophosphates; NMPs (mononucleotides)

24
Q

pyrmidines use _ and _ to interconvert between nucleobases and NMPs in 2 steps

A

phosphorylases and kinases

25
Q

have nucleoside but use phosphorylase, what are we making

A

removing sugar so making nucleobases from nucleosides (breakdown pathway)

26
Q

have nucleoside but use kinases, what are we making

A

adding a phosphate; makes NMPs ie convert nucleosides into nucleotides (salvage pathway)

27
Q

nucleotidases work to remove

A

phosphate to make nucleosides from nucleotides

28
Q

thymidine kinase 1 works to

A

make thymidine (nucleoside) into dTMP (nucleotide)

29
Q

why is viral thymidine kinase not as discriminating as human thymidine kinase, and what is the benefit of this?

A

viral thymidine will accept purines as well as T’s. The benefit is that make a drug (acyclovir) will not interact with human thymidine kinase so it will terminate synthesis of T’s in viral DNA

30
Q

purines use _ to interconvert between nucleobases and NMPs in one step

A

phosphoribosyltransferases

31
Q

phosphoribosyltransferases do what?

A

remove phosphate (interchange between nucleobases and NMPs)

32
Q

adenine phosphoribosyltransferases makes:

A

AMP

33
Q

HGPRT makes:

A

IMP/GMP

34
Q

hypoxanthine is the precursor for

A

IMP (purines)

35
Q

nitrogenous bases can be broken down into (2)

A
  1. uric acid

2. B-ureidopropionic acid

36
Q

uric acid is the final product of

A

purine catabolismm

37
Q

B-ureidopropionic acid is the final product of

A

pyrmidine catabolism

38
Q

uric acid like glutathione is an _

A

antioxidant

39
Q

T/F: uric acid/urate is soluble

A

FALSE insoluble

40
Q

how does gout occur?

A

uric acid crystals collecting in joints

41
Q

what is one pathology for gout

A

HPRT deficiency; cannot salvage nucleobases of purines

42
Q

how does SCID occur?

A

deficiency of adenosine deaminase; breakdown is not functional. dAMP into dATP is inhibited and dAMP accumulates. Inhibition of ribonucleotide reductase so foward rxn and thus no DNA synthesis