Nucleotide Metabolism Flashcards

0
Q

What are the three structures of a nucleotide?

A

Pentose sugar, nitrogenous base, phosphates

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1
Q

What are polymers of nucleotides?

A

Nucleic acids

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2
Q

What is a base + sugar?

A

nucleoside

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3
Q

What are the two purines?

A

adenine and guanine

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4
Q

What are the three pyrimidines?

A

thymine, cytosine, and uracil

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5
Q

What are some of the uses of nucleotides? (5)

A
  1. Energy currency
  2. Phosphate source
  3. Coenzymes
  4. Substrate activators
  5. 2nd messengers
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6
Q

What is an important intermediate in the biosynthesis of purines?

A

PRPP

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7
Q

PRPP is formed from ribose-5-phosphate. What enzyme is used? Activator? Inhibitor?

A

PRPP synthetase; inorganic phosphate; ADP

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8
Q

The base of what is built upon a molecule of PRPP?

A

A purine ring

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9
Q

Where do the carbons in a purine ring come from?

A

glycine, folate derivatives, and CO2

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10
Q

Where do the nitrogens in a purine ring come from?

A

glycine, aspartate, and glutamine

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11
Q

What is the first purine formed in the ten-step process?

A

IMP - inosine monophosphate

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12
Q

How many high energy bonds are required in purine synthesis?

A

6

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13
Q

AMP and GMP are formed from what?

A

IMP

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14
Q

What amino acid provides a nitrogen to IMP in the formation of adenosine?

A

aspartate

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15
Q

In the formation of guanosine, glutamine provides a nitrogen to what?

A

xanthosine

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16
Q

Where are the enzymes that construct the purine ring system?

A

cytosol, namely the liver, which secretes free bases and nucleosides

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17
Q

What are the first two steps of purine synthesis?

A

PRPP sythesis and amidotransferase

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18
Q

What is the committed step of purine synthesis?

A

2nd step - PRPP amidotransferase

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19
Q

What cells are reliant on purine recycling?

A

brain, lymphocytes, neutrophils

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20
Q

Purine rings are recycled by what?

A

re-attachment to PRPP

21
Q

In purine recycling Adenine phosphoribosyl transferase forms what from adenine?

A

AMP

22
Q

In purine recycling hypoxanthine-guanine phosphoribosyl transferase (HGPRT) recycles H and G to form what?

A

Hypoxanthine > IMP

Guanine > GMP

23
Q

What are the original ring components of pyrimidines?

A

glutamine, aspartate, and CO2

24
Q

What enzyme forms UMP?

A

CPS-II carbomoyl phosphate synthetase

25
Q

Where is UMP formed?

A

Cytosol and mitochondria

26
Q

What is required in the formation of CTP from UTP?

A

glutamine

27
Q

Deoxyribonucleotides are formed by reduction of what?

A

ribonucleotide disphosphates

28
Q

What is the product of purine breakdown?

A

Uric acid

29
Q

What is the key enzyme in the degradation of purines and pyrimidines?

A

Xanthine oxidase

30
Q

What are the cofactors in the degradation of purines and pyrimidines?

A

O2, molybdenum, iron, sulfur

31
Q

Beta-alanine and beta-aminoisobutyrate are the final products of what?

A

pyrimidine degradation

32
Q

What are used to treat neoplasms?

A

Inhibitors of nucleotide metabolism

33
Q

We don’t store nucleotides, so what happens if we have extra?

A

They get degraded

34
Q

What are the three inhibitors of nucleotide metabolism?

A

Structural analog, antifolates, glutamine antagonists

35
Q

What is a folic acid analog?

A

methotrexate

36
Q

Gout results from what?

A

Deposition of sodium urate crystals in the joints and kidneys

37
Q

What is defective in gout? (2)

A

PRPP synthetase is abnormal in some cases; HGPRT may be partially deficient in others

38
Q

In gout, leukocytes take up crystals and what happens next?

A

They rupture, releasing lysosomal enzymes which inflame and erode joints. Uric acid crystals in the kidney impair renal function

39
Q

What blocks formation of uric acid crystals through suicide inhibition of xanthine oxidase?

A

Allopurinol

40
Q

de novo purine synthesis is decreased by the reaction of what two things?

A

PRPP with allopurinol

41
Q

What is an anti-inflammatory used to reat gout which inhibits leukocyte movement?

A

Colchicine

42
Q

What inhibits organic ion transport? (gout)

A

Probenicid

43
Q

What condition is associated with x-linked recessive, deficiency of HGPRT activity?

A

Lesch-Nyhan syndrome

44
Q

In lesch-nyhan syndrome, intracellular levels of PRPP increase, IMP and GMP decrease. What does this lead to?

A

Increase in de novo purine synthesis

45
Q

What are some of the symptoms of lesch-nyhan syndrome?

A

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

46
Q

PRPP cannot react with allopurinol, so in treating lesch-nyhan syndrome, de novo purine synthesis does not decrease. What is reduced? What is not reduced?

A

gout; mental symptoms

47
Q

What is deficient in glycogen storage disease type I (von gierke’s)?

A

Glucose-6-phosphatase

48
Q

What two things are increased in glycogen storage disease type I (von Gierke’s)?

A

ribose-5-phosphate and PRPP

49
Q

In glycogen storage disease type I (von gierke’s) is de novo purine synthesis increased or decreased?

A

increased

50
Q

What condition is associated with the following?:

  1. defective conversion of orotate or orotidine monophosphate to UMP
  2. reduced DNA and RNA synthesis results leading to sever anemia
  3. treatment with uridine can be effective
A

Orotic aciduria