Purine and Pyrimidine Metabolism Flashcards

1
Q

What are nucleosides?

A

They are bases with the sugar group attached

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2
Q

What are nucleotides?

A

They are bases with the sugar group AND phosphate group(s)

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3
Q

What are the purines?

A

Adenine and guanine (2 rings)

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4
Q

What are the pyrimidines?

A

Cytosine, uracil and thymine (1 ring)

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5
Q

What is the order of purine biosynthesis?

A

The purine ring is built atom by atom onto the ribose group

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6
Q

What are the constituents that make up the purine ring?

A
  • Aspartate
  • Glycine
  • Glutamine
  • CO2
  • N^10-Formyl-FH4
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7
Q

What is the first step of purine ring synthesis?

A

Ribose-5-Phosphate -> PRPP

R-5-Pi is activated

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8
Q

What is the second step of purine ring synthesis?

A

PRPP -> 5-phosphoribosylamine

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9
Q

Which is the regulated step of purine ring synthesis?

A

The second step:

PRPP -> 5-phosphoribosylamine

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10
Q

What is the enzyme catalyzing this reaction:

PRPP -> 5-phosphoribosylamine

A

Glutamine PRPP Amidotransferase

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11
Q

Where does ribose-5-phosphate in purine synthesis come from?

A

Pentose Phosphate Pathway

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12
Q

What nucleotide can branch into GMP or AMP?

A

IMP (inosinic acid)

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13
Q

How does allosteric inhibition of Glutamine PRPP Amidotransferase occur?

A

AMP and GMP are allosteric inhibitors of Glutamine PRPP Amidotransferase -> so it is negative feedback from the products

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14
Q

What is the function of 6-mercaptopurine?

A

It is an anti tumor agent that functions because it is converted into a nucleotide that will inhibit various steps of the purine synthesis, including Step 2, the rate limiting step

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15
Q

What are the constituents that make up the pyrimidine ring?

A
  • Aspartate
  • Glutamine
  • CO2
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16
Q

What is the synthesis order of the pyrimidine ring?

A

Pyrimidine ring is synthesized FIRST separately from the ribose-5-phosphate and then it is attached to it

17
Q

What is the regulated step of pyrimidine synthesis?

A

Glutamine + CO2 + ATP -> Carbamoyl Phosphate

18
Q

What is the enzyme catalyzing the rate limiting step of pyrimidine synthesis?

A

Carbamoyl phosphate synthetase II

19
Q

What is the pyrimidine precursor?

A

UMP

20
Q

How does leflunomide treat arthritis?

A

Blocks pyrimidine synthesis by blocking dihydroorotate dehydrogenase

21
Q

What enzyme converts dUMP to dTMP?

A

Thymidylate Synthase

22
Q

What is the source of the methyl group for the conversion of dUMP to dTMP?

A

N^5/N^10-methylene THF

23
Q

How does the anti tumor drug 5-fluorouracil work?

A

It is converted to f-dUMP which covalently binds to thymidylate synthase and inhibits the conversion of dUMP to dTMP.

24
Q

What is the advantage of 5-fluorouracil in its side effects on normal cells?

A

As it only affects the conversion of dUMP, DNA synthesis is inhibited while RNA synthesis remains in tact.

25
Q

How does the anti tumor agent methotrexate function?

A

It functions by inhibiting the function of dihydrofolate reductase which prevents the conversion of dihydrofolate to THF. This results in an accumulation of DHF which is toxic to the cell.

26
Q

What is the function of ribonucleotide reductase?

A

It acts on the ribonucleotide-5’-diphosphate to form deoxyribonucleotide-5’-diphosphate

27
Q

What is the cofactor necessary for the reaction catalyzed by ribonucleotide reductase?

A

Thioredoxin

28
Q

Which hydroxyl group of ribose is converted to hydrogen?

A

2’ group

29
Q

What is a drug that acts as an inhibitor of ribonucleotide reductase?

A

Hydroxyurea

30
Q

What is the function of HGPRTase?

A

There are 2 reactions:

Hypoxanthine + PRPP -> IMP + PPi
Guanine + PRPP -> GMP + PPi

31
Q

What is deficient in Lesch-Nyhan Syndrome?

A

HGPRTase

32
Q

What is HGPRTase?

A

Hypoxanthine-Guanine Phosphoribosyltransferase

33
Q

What is the final product of purine degradation in humans?

A

Uric Acid

34
Q

What is the enzyme that converts hypoxanthine to xanthine and xanthine to uric acid?

A

Xanthine Oxidase

35
Q

What is uric acid found as in blood?

A

Urate

36
Q

What are some consequences of overproduction or under secretion of uric acid?

A

Gout

37
Q

How does allopurinol work to treat gout?

A

It inhibits xanthine oxidase so that less uric acid is fomed