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biochemistry > Nucleotide metabolism > Flashcards

Nucleotide metabolism Flashcards

1
Q

What are the 4 roles of RNA?

A
  • genetic material of some virus
  • template of genetic info for protein synth
  • couple RNA template to protein synth
  • component of ribosomes
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2
Q

What are the two pentose sugars?

A
  • ribose

- deoxyribose, it has an H instead of OH at C-2

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3
Q

What are the two types of nitrogenous bases?

A
  • purine - adenine, guanine

- pyrimidines - thymine, cytosine, uracil

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4
Q

What is a nucleoside?

A

base and sugar

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5
Q

what is a nucleotide

A

base, sugar, and phosphate

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6
Q

What is the important intermediate for purine biosynthesis?

A

PRPP

5 phosphoribsyl-1-phrophosphate

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7
Q

What is PRPP formed from?

A

Ribose 5 phosphate

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8
Q

what enzyme makes PRPP from ribose 5 phosphate?

A

PRPP synthetase

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9
Q

what activates PRPP synthetase?

A

inorganic phosphate

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10
Q

What inhibits PRPP synthetase?

A

ADP

?- if there is lots of ADP that means there is less enerty

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11
Q

What is the first difference between purine and pyrimidine synthesis?

A

Purine - base is built upon PRPP, a sugar

Pyramidine - build base then add sugar

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12
Q

What are the 3 places CARBONS are derived from to make a purine?

A
  • glycine
  • folate derivative
  • CO2
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13
Q

Purine, what are the 3 places NITROGENS come from?

A
  • glycine
  • glutamine
  • aspartate
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14
Q

How many steps to build the ring on the sugar in purine synthesis?

A

10 step process

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15
Q

what is the first purine formed?

A

IMP

inosine monophosphate

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16
Q

How many high energy bonds to make IMP, inosine monophosphate?

A

6 high energy bonds

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17
Q

what two things are formed from IMP?

A
  • AMP

- GMP

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18
Q

What provides the Nitrogen in the formation of AMP?

A

-Aspartate + IMP = adenosine monophosphate

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19
Q

What provides the Nitrogen in the formation of GMP?

A

-Glutamine + xanthosine = GMP

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20
Q

What is the committed step of purine synthesis?

A

The first step, PRPP gets its first Nitrogen addition via glutamine and amido transferase

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21
Q

What are the two paths after IMP is formed?

A
  • add asparte and GTP and your get AMP

- add NAD to get XMP, then at glutamine to get GMP

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22
Q

What regulates GMP synthesis?

A

APT

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23
Q

what regulates AMP synthesis?

A

GTP

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24
Q

what is the purine made from IMP called?

A

hypoxanthine

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25
Q

What inhibits purine synthesis?

A

AMP

GMP

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26
Q

How are purine rings recycles?

A

Through re-attachment to PRPP if the base has been separated from the sugar

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27
Q

What is added to PRPP to get IMP?

A

Hypoxanthine, a purine

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28
Q

What is the location of most of the recycling of purines?

A
  • brain

- lymphocytes

29
Q

What enzyme attaches guanine or hypoxanthine back to PRPP? …..recycles guanine and hypoxanthine

A

HGPRT

-hypoxyanthine-guanine phosphoribosyl transferase

30
Q

What recycles adenine, adding it back to PRPP?

A

APRT

-aenine phosphoriboxyl transferase

31
Q

What does enzyme adenine phosphoribosyl transferase do?

A

recycles adenine into AMP

32
Q

What does hyposyanthine-guanine phosphoribosyl transferase do?

A

recycle hypoxanthine and guanine back into IMP

33
Q

What donates CARBON components pyramidines?

A
  • glutamine
  • aspartate
  • CO2
34
Q

What donates NITROGEN components to pyramidines?

A
  • glutamine

- aspartate

35
Q

What enzyme forms Uridine monophosphate? UMP

A

carbamoyl phosphate synthetase II,

- CPS II

36
Q

Where does CPS II work making UMP?

A

In the cytosol and mitochondria

37
Q

In what order are pyrimidines made?

A

ring first, then add sugar

38
Q

what is required to form CTP from UMP?

A

Glutamine

- CTP synthase

39
Q

What are the locations for pyrimidine synthesis?

A
  • 1 cytosol - CPS II
  • outer surface of inner membrane mitochondria
  • back to cytosol
40
Q

what is the initial pyrimidine nucleotide?

A

UMP

41
Q

How are uracil and thymine recycled?

A

by two sequential reactions

42
Q

Uracil + ribose 1 phosphate -> ?

A

Uridine + pi

43
Q

Uridine + ATP -> ?

A

UMP + ADP

44
Q

how are deoxyribonucleotides formed?

A

by the reduction of ribonucleotides diphosphates by ribonucleotide reductase.

45
Q

Does our body store nucleotides?

A

Nope

46
Q

What is the product of Purine breakdown?

A

Uric acid

47
Q

what is the key enxyme in purine breakdown?

A

xanthine oxidase

48
Q

what coenxymes/cofactors does xanthine oxidase require? There are 4/

A
  • O2
  • molybdenum
  • Fe
  • Sulfer
49
Q

What nucleotides can act a an energy source?

A

pyramidines

50
Q

Why can purines serve as energy source

A

Because it becomes uric acid that either crystalizes or is excreated via the urine.

51
Q

guanosine path to urine?

A
  • guanosine
  • guanine
  • xanthine - xanthine oxidase
  • uric acid
  • urine
52
Q

AMP to urine?

A
  • AMP
  • IMP
  • inosine
  • hypoxyanthine - xanthine oxidase
  • xanthine - xanthine oxidase
  • uric acid
  • urine
53
Q

What can degredation of purines lead to?

A

Gout if the uric acid crystalized.

54
Q

Why does pyramidine degredation not lead to gout?

A

because the products are water soluble

  • B- alanine
  • B - aminoisoburyrate
55
Q

why can some of the pyramidine degredation products get used as a metabolic fuel source?

A

because b-alanine can further convert to malonate/malonic acid
b-aminoisobuterate -> methmalonal used in odd chain FA synthesys.

56
Q

What are inhibitors of nucleotide metabolism used for?

A

nucleotide inhibitors are used to treat neoplasms

57
Q

What inhibids synthesis of deoxythymidine monophosphate?

A

methotrexate - prevents dihydrofolate to tetrahydrofolate.

58
Q

How does 5-flourouracil work?

A

it inhibits enzyme, thymidylate synthase that turns dUMP to dTMP

59
Q

What can cause gout?

A
  • PRPP synthetase - make too much purines
  • ## HGPRT - partially deficient (recycle enzyme)
60
Q

What does gout do?

A

Uric acid crystals deposited within joints or kidney
leukocytes take up crystals, rupture inflaming joints
kidney crystals impair function

61
Q

How does allopurinol block to formation of uric acid?

A

suicide inhibition of xanthine oxidase ( degrades purines)

62
Q

How is gout treated?

A
  • inhibit xanthine oxidase (purine degrader)
  • decrease new purine synthsis
  • inhibit leukocyte movement so they cant degrade joints.
63
Q

how could we decrease de novo purine synthesis?

A

reacting PRPP (first building block of purine synth) with allopurinol so it becomes oxypurinol instead.

64
Q

What is lesch nayan syndrome?

A

X-linked deficiency of HGPRT activity (Recyclying of purines)

65
Q

What are the symptoms of lesch -Nyhan syndrome?

A
  • gout
  • hyperuricemia
  • urinary tract stones
  • mental retardatons
  • self-mutilations
  • spasticity
66
Q

In Lesch-Nyhan syndrome with the HGPRT deficiency what happens?

A
  • Intracellular levels of PRPP increase - the base for purines
  • IMP and GMP decrease (IMP first purine formed)
  • de novo purine synthesis increases because none are getting recycled.
67
Q

What is glycogen storage disease?

A

deficient Glucose 6 phosphate
Ribose 5 phosphate and PRPP increase (purine base)
increase in purine synthesis

68
Q

What is orotic aciduria?

A

devective conversion of orotate or orotidine monophosphate to UMP - (pyridine)

69
Q

What does orotic aciduria cause?

A
  • reduced DNA RNA synthesis leading to anemia

- can treat with uridine.

biochemistry (13 decks)

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