Nucleotide Metabolism Flashcards

1
Q

What is a nucleoside

A

Base+sugar

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2
Q

What is a nucleotide

A

Base+sugar+phosphate(s)

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3
Q

What are the purines

A

Adenine and guanine

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4
Q

What are the pyrmidines

A

Thymine, cytosine, uracil

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5
Q

What are 5 uses of nucleotides

A
  1. energy currency 2. phosphate source 3. coenzyme 4. substrate activator 5. 2nd messengers
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6
Q

What are some complexes that adenosine is part of

A

SAM, NAD, FAD, cAMP

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7
Q

What is the source of ribose 5-phosphate

A

pentose pathway

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8
Q

What converts ribose 5-phosphate to PRPP

A

PRPP synthetase

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9
Q

What is the function of PRPP

A

purine ring is built with it as a base, and it is added to orotate to make pyrimidines

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10
Q

What inhibits PRPP synthetase; what activates it

A

ADP (end product inhibition); Pi

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11
Q

What are the Nitrogen sources for purines

A

Glycine, aspartate, glutamine

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12
Q

What are the carbon sources for purines

A

glycine, folate derivatives, and CO2

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13
Q

What is the first purine formed

A

IMP inosine monophosphate

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14
Q

What is the energy requirement to build a purine ring

A

6 high energy bonds

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15
Q

What is IMP a precursor for

A

AMP and GMP

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16
Q

What is the nitrogen donor to convert IMP to AMP

A

Aspartate

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17
Q

What is the nitrogen donor to convert IMP to GMP

A

Glutamine

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18
Q

Where does purine synthesis take place

A

In the cytosol, prominent in the liver which exports free bases and nucleosides

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19
Q

What is the committed step in purine synthesis

A

The first one in which amidotransferase swaps NH3 in for 2 Pi

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20
Q

How are purine rings recycled

A

By being re-attached to PPRP

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21
Q

Where is purine recycling most prominent

A

In lymphocytes, PMN, brain tissue. They don’t have the resources to make precursors

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22
Q

What is HGPRT

A

enzyme that recycles guanine and hypoxanthine

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23
Q

What is APRT

A

Enzyme that recycles adenine to AMP

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24
Q

What are the nitrogen sources for pyrimidines

A

Glutamine, aspartate

25
Q

What are the carbon sources for pyrimidines

A

Aspartate and CO2

26
Q

What is the location for the formation of UMP

A

Cytosol except for step 3 (oxidation) happens in on the outer surface of the inner mito membrane

27
Q

What are the enzymes involved in uridine formation

A

CPS II, CPS I, transferase/decarboxylase complex

28
Q

What is the enzyme for converting UTP to CTP

A

CTP synthase with glutamine for the N source

29
Q

What enzyme forms deoxyribonucleotides

A

Ribonucleotide reductase

30
Q

What is the product of purine degradation

A

uric acid

31
Q

What enzyme and cofactors are involved in purine degradation

A

Xanthine oxidase; O2, molybdenum, iron, sulfur

32
Q

What is the difference between a catalytic site and an activity site

A

Catalytic is where the conversion happens, activity site affects the speed of the conversion

33
Q

What affects the activity of ribonucleotide reductase

A

ATP speeds it up, dATP slows it down

34
Q

How does ribonucleotide reductase switch to reducing different nucleotides

A

product feedback causes it to ‘class switch’ to a different nucleotide

35
Q

Why does gout happen if someone has an overactive PRPP synthetase

A

Overproduction and thus over degradation of purines. Uric acid is not very water soluble, so high levels will cause it to precipitate into crystals in tissue

36
Q

What are the breakdown products of cytosine and uracil

A

Beta-alanine which can be converted into malonate

37
Q

what is malonate used for

A

Fatty acid synthesis

38
Q

What is the breakdown product of thymine

A

beta isobutyrate which can be converted into methylmalonate

39
Q

What is methylmalonate used for

A

It is metabolism for energy as an odd chain fatty acid

40
Q

What are 3 classes of nucleotide inhibitors

A
  1. structural analogs 2. antifolates 3. glutamine antagonists
41
Q

What class of nucleotide inhibitors is 5-fluoroucil

A

structural analog for uracil; it block the formation of dTMP

42
Q

What class of nucleotide inhibitors is methotrexate

A

anti folate; it blocks the regeneration of FH4 and synthesis of dTMP via dihydrofolate reductase

43
Q

What enzyme is involved in converting dUMP into dTMP

A

thymidylate synthase

44
Q

What does allopurinol do

A

suicide inhibition of xanthine oxidase to stop uric acid formation and react with PRPP to stop de novo synthesis of purines

45
Q

What does probenecid do

A

inhibits the organic ion transporter in the kidney so that it doesn’t reabsorb uric acid

46
Q

what does colchicine do

A

anti-inflammatory by inhibiting leucocyte movement

47
Q

Why does gout happen if someone has a partially deficient HGPRT

A

Because purines are not being recycled, they get degraded

48
Q

What is the pKa of uric acid

A

5.4

49
Q

What causes Lesch-Nyhan Syndrome

A

X-lined recessive, deficiency of HGPRT activity

50
Q

What happens to the cell in Lesch-Nyhan syndrome

A

PRPP levels rise, IMP and GMP decrease, de novo purine synthesis increases

51
Q

What are symptoms of Lesch-Nyhan syndrome

A

Self-mutilation, gout, hyperuricemia, mental retardation, spasticity, urinary tract stones

52
Q

What medications are taken for Lesch-Nyhan syndrome

A

allopurinol to reduce gout, but there is nothing to reduce the overproduction of purines

53
Q

What causes von Gierke’s diease (glycogen storage disease type I)

A

Glucose-6-phosphatase is deficient

54
Q

What happens to the cell in von Gierke’s disease

A

ribose-5-phosphate and PRPP increase, increased de novo purine synthesis

55
Q

What causes orotic aciduria

A

Defective conversion of orotate or OMP to UMP

56
Q

What happens to the cell in orotic aciduria

A

Reduced DNA and RNA synthesis which results in severe anemia

57
Q

What treatments are recommended for orotic aciduria

A

treatment with uridine can be effective

58
Q

What does glucose-6-phosphotase do

A

cleave phosphate off glucose-6-phosphate to make Pi and glucose; final step of gluconeogenesis and glycogenolysis