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BMB 402 > Chapter 18: Nucleotide Metabolism > Flashcards

Chapter 18: Nucleotide Metabolism Flashcards

1
Q

What are nucleotides used in?

A
  • energy conversion reactions
  • signal transduction pathways
  • coenzyme-dependent reactions
  • genetic information storage and transfer
  • can be a target of immunosuppressants and anti-cancer drugs
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2
Q

What do nucleotides consist of?

A
  • nucleotide base (pyrimidine or purine)
  • ribose ring
  • phosphoryl group
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3
Q

What are the purines?

A

Adenine
Guanine

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4
Q

What are the pyrimidines?

A

Cytosine
Thymine
Uracil

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5
Q

What is the most abundant nucleotide?

A

ATP

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6
Q

Why is the nucleotide salvage pathway important?

A
  • used to resynthesize nucleotide monophosphates from free bases
  • energy investment is not as high as the de novo pathway
  • PRPP is produced
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7
Q

What common intermediate is produced during purine metabolism?

A

inosine-5’-monophosphate (IMP)

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8
Q

What is a major difference between purine and pyrimidine biosynthesis?

A

In purine biosynthesis, the base is built directly on the ribose.

In pyrimidine biosynthesis, the base is built and then the ribose is added.

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9
Q

What happens in stage 1 of purine synthesis?

A

Ribose-5-P is converted to PRPP by PRPP synthetase. It goes through the pathway until AIR synthetase adds the first ring to the ribose, making AIR.

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10
Q

What happens in stage 2 of purine synthesis?

A

AIR continues down the pathway until IMP is made by IMP synthase.

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11
Q

What is hypoxanthine?

A

the purine base

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12
Q

What is the significance of IMP?

A

It is a molecule that serves as a divergence point for making different purines as well as a feedback molecule for the pathway itself.

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13
Q

What can IMP be used to produce?

A

AMP and GMP

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14
Q

What do AMP and GMP create?

A

nucleoside triphosphates for RNA and DNA synthesis

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15
Q

How is GTP made?

A

GMP is converted to GDP by guanylate kinase. Then, GDP is converted to GTP by nucleoside diphosphate kinase. GTP can then be used to make RNA.

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15
Q

How is ATP made?

A

AMP is converted to ADP by adenylate kinase. Then, ADP is converted to ATP by nucleoside diphosphate kinase. ATP can then be used to make RNA.

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16
Q

What enzyme is used to make nucleoside triphosphates?

A

Nucleoside diphosphate kinase

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17
Q

What enzyme is responsible for the formation of deoxy nucleotides?

A

Ribonucleotide reductase

it converted ADP and GDP to dADP and dGDP

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18
Q

How are dADP and dGDP converted to dATP and dGTP to be used in DNA synthesis?

A

Nucleoside diphosphate kinase

19
Q

What does ADP inhibit in the purine synthesis pathway?

A

PRPP synthetase

20
Q

What is uric acid a product of?

A

purine degradation

21
Q

How is uric acid removed from the body?

A

It is excreted directly or further metabolized to nitrogen waste products

22
Q

What is gout?

A

A disease caused by a defect in the purine degradation pathway. It is caused by a buildup of uric acid crystals in the joints and kidneys. Often times, the uric acid crystals build up in the joint of the big toe.

It results in an increase of PRPP synthetase and an overproduction IMP.

23
Q

A deficiency in what enzyme results in SCID?

A

adenosine deaminase

24
Q

A deficiency in HGPRT can lead to what disease?

A

Lesch-Nyhan syndrome

25
Q

What does HGPRT do?

A

It is an enzyme that is used to salvage hypoxanthine and guanine bases

26
Q

What is Lesch-Nyhan Syndrome?

A

A disease with neurologic symptoms, including severe anxiety and self-mutilation. It is an X-linked recessive genetic mutation. (more prevalent in men)

It results from a deficiency in the HGPRT enzyme.

27
Q

What is SCID?

A

Severe combined immunodeficiency disease - severely defective immune system resulting from low levels of functional B and T cells

Only treatment is a bone marrow transplant

Increased adenosine leads to increased dATP. Ribonucleotide reductase is inhibited and cells are starved on dNTPs.

Is a result of a deficiency in adenosine deaminase.

28
Q

What are all of the atoms derived from in pyrimidine metabolism?

A

aspartate or carbamoyl acid

29
Q

What is the main product of pyrimidine biosynthesis?

A

Uridine-5’-monophosphate (UMP)

30
Q

What is UMP used to make?

A

It is converted to CTP by CTP synthase. The carbonyl oxygen is replaced by NH2 from glutamine.

31
Q

What are positive allosteric activators of pyrimidine biosynthesis?

A

PRPP and ATP

32
Q

What are negative allosteric activators of pyrimidine biosynthesis?

A

CTP, UTP, and UPD

32
Q

What are the products of pyridine degredation?

A

Beta-Alanine
Beta-Aminoisobutyrate
NH4+
HCO3-

33
Q

What is 5-Fluorouracil?

A

A potent anticancer medication that prevents the conversion of dUMP to dTMP (thymidylate synthesis).

5FU inhibits DNA synthesis in cancer cells.

34
Q

Why must patients be screened for dihydropyrimidine dehydrogenase deficiency before being put on 5-Fluorouracil?

A

A deficiency in this enzyme prevents the drug from being degraded, causing it to buildup to severely toxic levels

35
Q

What does ribonucleotide reductase require to catalyze the formation of deoxynucleotides?

A

two electrons from NADPH, which are used to reduce a pair of sulfhydryls in the enzyme’s active site

36
Q

What is the net equation of deoxynucleotide formation?

A

NADPH + H+ + Nucleoside-5’-diphosphate —> H2O + Deoxynucleoside-5’-disphosphate + NADP+

37
Q

What is required for the synthesis of thymidylate?

A

The addition of a methyl group

38
Q

What is dUMP a source for?

A

thymidylate (dTMP)

39
Q

What can inhibit thymidylate synthesis?

A

Uracil-based compounds can block the activity of thymidylate synthase.

5-Fluorouracil and 5-Fluorodeoxyuridine are examples

Other anticancer drugs like Methotrexate block the formation of the methyl donor that is required to form thymidylate.

40
Q

What deoxynucleotide does ribonucleotide reductase NOT make?

A

deoxy-T

41
Q

Why are anticancer cocktails preferred over use of just one drug?

A

Each drug blocks a specific process in order to maximize chances of killing the cancer cells before drug resistance begins.

42
Q

Uric acid is an example of a _____

A

purine

43
Q

Which nucleotide is required to make AMP?

A

GTP

BMB 402 (14 decks)

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