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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
What inhibits purine synthesis?
AMP | GMP
26
How are purine rings recycles?
Through re-attachment to PRPP if the base has been separated from the sugar
27
What is added to PRPP to get IMP?
Hypoxanthine, a purine
28
What is the location of most of the recycling of purines?
- brain | - lymphocytes
29
What enzyme attaches guanine or hypoxanthine back to PRPP? .....recycles guanine and hypoxanthine
HGPRT | -hypoxyanthine-guanine phosphoribosyl transferase
30
What recycles adenine, adding it back to PRPP?
APRT | -aenine phosphoriboxyl transferase
31
What does enzyme adenine phosphoribosyl transferase do?
recycles adenine into AMP
32
What does hyposyanthine-guanine phosphoribosyl transferase do?
recycle hypoxanthine and guanine back into IMP
33
What donates CARBON components pyramidines?
- glutamine - aspartate - CO2
34
What donates NITROGEN components to pyramidines?
- glutamine | - aspartate
35
What enzyme forms Uridine monophosphate? UMP
carbamoyl phosphate synthetase II, | - CPS II
36
Where does CPS II work making UMP?
In the cytosol and mitochondria
37
In what order are pyrimidines made?
ring first, then add sugar
38
what is required to form CTP from UMP?
Glutamine | - CTP synthase
39
What are the locations for pyrimidine synthesis?
- 1 cytosol - CPS II - outer surface of inner membrane mitochondria - back to cytosol
40
what is the initial pyrimidine nucleotide?
UMP
41
How are uracil and thymine recycled?
by two sequential reactions
42
Uracil + ribose 1 phosphate -> ?
Uridine + pi
43
Uridine + ATP -> ?
UMP + ADP
44
how are deoxyribonucleotides formed?
by the reduction of ribonucleotides diphosphates by ribonucleotide reductase.
45
Does our body store nucleotides?
Nope
46
What is the product of Purine breakdown?
Uric acid
47
what is the key enxyme in purine breakdown?
xanthine oxidase
48
what coenxymes/cofactors does xanthine oxidase require? There are 4/
- O2 - molybdenum - Fe - Sulfer
49
What nucleotides can act a an energy source?
pyramidines
50
Why can purines serve as energy source
Because it becomes uric acid that either crystalizes or is excreated via the urine.
51
guanosine path to urine?
- guanosine - guanine - xanthine - xanthine oxidase - uric acid - urine
52
AMP to urine?
- AMP - IMP - inosine - hypoxyanthine - xanthine oxidase - xanthine - xanthine oxidase - uric acid - urine
53
What can degredation of purines lead to?
Gout if the uric acid crystalized.
54
Why does pyramidine degredation not lead to gout?
because the products are water soluble - B- alanine - B - aminoisoburyrate
55
why can some of the pyramidine degredation products get used as a metabolic fuel source?
because b-alanine can further convert to malonate/malonic acid b-aminoisobuterate -> methmalonal used in odd chain FA synthesys.
56
What are inhibitors of nucleotide metabolism used for?
nucleotide inhibitors are used to treat neoplasms
57
What inhibids synthesis of deoxythymidine monophosphate?
methotrexate - prevents dihydrofolate to tetrahydrofolate.
58
How does 5-flourouracil work?
it inhibits enzyme, thymidylate synthase that turns dUMP to dTMP
59
What can cause gout?
- PRPP synthetase - make too much purines - HGPRT - partially deficient (recycle enzyme) -
60
What does gout do?
Uric acid crystals deposited within joints or kidney leukocytes take up crystals, rupture inflaming joints kidney crystals impair function
61
How does allopurinol block to formation of uric acid?
suicide inhibition of xanthine oxidase ( degrades purines)
62
How is gout treated?
- inhibit xanthine oxidase (purine degrader) - decrease new purine synthsis - inhibit leukocyte movement so they cant degrade joints.
63
how could we decrease de novo purine synthesis?
reacting PRPP (first building block of purine synth) with allopurinol so it becomes oxypurinol instead.
64
What is lesch nayan syndrome?
X-linked deficiency of HGPRT activity (Recyclying of purines)
65
What are the symptoms of lesch -Nyhan syndrome?
- gout - hyperuricemia - urinary tract stones - mental retardatons - self-mutilations - spasticity
66
In Lesch-Nyhan syndrome with the HGPRT deficiency what happens?
- 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
What is glycogen storage disease?
deficient Glucose 6 phosphate Ribose 5 phosphate and PRPP increase (purine base) increase in purine synthesis
68
What is orotic aciduria?
devective conversion of orotate or orotidine monophosphate to UMP - (pyridine)
69
What does orotic aciduria cause?
- reduced DNA RNA synthesis leading to anemia | - can treat with uridine.

biochemistry (13 decks)

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