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Danielle- MCM Test 1 > Lecture 7: Nucleotide Metabolism > Flashcards

Lecture 7: Nucleotide Metabolism Flashcards

1
Q

Nucleotides are phosphate __________ of nucleosides

A

Esters

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2
Q

What does a nucleotide contain?

A

Base, sugar, and a phosphate

Nucleoside = no phosphate

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3
Q

What enzyme makes deoxyribose?

A

Ribonucleotide reductase

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4
Q

What is the nucleotide abbreviation and nucleoside name for hypoxanthine?

A

Nucleoside name = inosine

Nucleotide abbreviation = IMP

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5
Q

What is the nucleotide abbreviation and the nucleoside name for xanthine?

A

Nucleoside name = xanthosine

Nucleotide abbreviation = XMP

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6
Q

CoA, cAMP, NAD and FAD are all examples of what?

A

Nucleotides

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7
Q

What are the sources of ring atoms for purines?

A

CO2, Gln, Gly, Asp, N10-formyl THF

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8
Q

What are the sources of ring atoms in pyrimidines?

A

HCO3-, Gln, Asp, N5, N10-methylene THF

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9
Q

___________ are synthesized attached to ribose hostage. The ribose initially contributed by PRPP. The sugar is already there and you want to build the base onto it

A

Purines

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10
Q

What is the committed step of purine synthesis?

A

Formation of the phosphoribosyl amine (addition of amine group creating PRA)

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11
Q

What is the role of methotrexate?

A

It inhibits the enzyme that attaches the carbon from the folate to close the purine ring. This will then inhibit DNA synthesis

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12
Q

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

A

PPP

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13
Q

What stimulates PRPP synthetase in the first step of purine synthesis?

A

Phosphate

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14
Q

What inhibits PRPP synthetase in the first step of purine synthesis?

A

Purine nucleotides (GMP, AMP, IMP)

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15
Q

What stimulates the committed step of purine synthesis?

A

PRPP

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16
Q

What inhibits the committed step of purine synthesis?

A

Purine nucleotides (GMP, AMP, IMP)

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17
Q

What inhibits adenylosuccinate synthetase that converts IMP to adenylosuccinate monophosphate during purine synthesis?

A

AMP

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18
Q

What inhibits IMP dehydrogenase that converts IMP to XMP during purine synthesis?

A

GMP

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19
Q

What step of purine synthesis gives off fumarate?

A

Adenylosuccinate monophosphate -> AMP with the enzyme adenylosuccinase

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20
Q

What carbon in a purine base is donated from folate, closing the ring structure?

A

The 8th carbon, next to the amine group donated from glutamine in the committed step

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21
Q

AMP synthesis is stimulated by _______

A

GTP

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22
Q

GMP synthesis is stimulated by ______

A

ATP

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23
Q

__________ are synthesized by building the base first then adding your sugar.

A

Pyrimidines

  • Synthesized from carbamoyl phosphate and aspartate by ATCase
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24
Q

What stimulates the carbamoyl phosphate synthetase II in the first step of pyrimidine synthesis?

A

PRPP

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25
Q

What inhibits Carbamoyl phosphate synthetase II in the first step of pyrimidine synthesis?

A

UTP

26
Q

What is the regulated enzyme in pyrimidine synthesis and is necessary to build the base?

A

Aspartate transcarbamoylase (ACTase)

27
Q

What steps of pyrimidine synthesis occur in the mitochondria?

A

Dihydroorotate-> orotate with the enzyme dihydroorotate dehydrogenase

This enzyme only in the mito

28
Q

What drug can inhibit thymidylate synthase that converts dUMP -> dTMP in pyrimidine synthesis?

A

5-flurouracil

  • This is the step in pyrimidine synthesis that utilizes folate
29
Q

5-fluorouracil is a drug that is an analog of thymidilate synthase which is an enzyme that converts dUMP -> dTMP in pyrimidine synthesis. What is 5-fluorouracil good at curing?

A

Retroviruses

30
Q

There is a human hereditary disorder involving the synthesis of pyrimidine nucleotides called _______ _________

A

Orotic Aciduria

31
Q

What is used to treat orotic aciduria?

A

Oral uridine

32
Q

What feedback inhibits ATCase in pyrimidine synthesis?

A

CTP

33
Q

What stimulates ATCase in pyrimidine synthesis?

A

ATP

34
Q

What is the limiting factor for DNA synthesis?

A

dTTP

35
Q

What types of diseases is methotrexate used for?

A

Autoimmune disorders

Cancer therapy

36
Q

Methotrexate is an example of what type of inhibitor?

A

Strong competitive inhibitor

  • Very low kM so you have to be careful when prescribing it and give very low doeses
37
Q

What enzyme does methotrexate target?

A

Dihydrofolate reductase that converts in the liver

38
Q

Antibacterial agents such as ______ drugs act as competitive inhibitors of teh bacterial enzyme that incorporates p-aminobenzoic acid (PABA) into folate.

A

Sulfa

39
Q

What are sulfa drugs used for?

A

Used to inhibit the replication of viruses and bacteria

40
Q

What disease is caused by excess adenosine deaminase, which is the enzyme that converts adenosine -> inosine in purine catabolism?

A

Hemolytic anemia

  • You have a buildup of inosine
41
Q

What disease is caused by deficient levels of adenosine deaminase which is the enzyme that converts adenosine -> inosine in purine catabolism?

A

SCID

  • Causes a buildup of adenosine
42
Q

How does an overproduction of adenosine deaminase cause heymolytic anemia?

A

Increased degradation of adenosine depletes adenine nucleotide pool and triggers premature destruction of RBCs

43
Q

What is SCID?

A
  • Fatal genetic disorder in which both B and T cells of the adaptive immune system are defective
  • X-linked
44
Q

Gout most commonly affects the big toe. What is the anatomical name for this?

A

Metatarsal pharyngeal joint

45
Q

What is the role of urate oxidase?

A

Converts uric acid to soluble allantoin

46
Q

What is the role of colchicine?

A

A treatment used for gout. It decreases the movement of granulocytes to the affected area

47
Q

What is the role of probenecid?

A

Used in the treatment of gout. Increases excretion of uric acid

48
Q

In pyrimidine catabolism, what pyrimidines make ketogenic products and what are the products?

A

U’s and C’s make the ketogenic product malonyl CoA

49
Q

In pyrimidine catabolism what pyrimidines make glucogenic products and what are the products?

A

T’s make the glucogenic products methylmalonyl CoA and Succinyl CoA

50
Q

What is the role of uridine phosphorylase?

A

Converts uridine or deoxyuridine -> Uracil and Deoxythymidine -> thymine in pyrimidine catabolism

51
Q

How much energy is required to generate IMP in purine synthesis?

A

4 ATP

**1 more than pyrimidine synthess*

52
Q

How much energy is required to generate UMP?

A

3 ATP

53
Q

What is the role of dihydrofolate reductase?

A

Convert dihydrofolate (inactive) -> THF (active)

This is the enzyme that is inhibited by methotrexate

54
Q

What is the role of APRT (adenine phosphoribosyl-transferase)?

A

Used in the purine salvage pathway to convert adenine -> AMP

  • Uses PRPP as a cofactor
55
Q

What is the role of HGPRT?

A

Used in purine catabolism to convert Guanine and Hypoxanthine -> GMP or IMP

  • Uses PRPP as cofactor
56
Q

What is Lesch-Nyhan syndrome?

A

Defect in HGPRT enzyme in purine salvage pathway

  • Overproduction of uric acid -> Pts have primary hyperuricemia and hyperuricosuria leading to gout
57
Q

What are the symptoms of Lesch-Nyhan syndrome?

A

defect in HGPRT

Urate kidney stones, poor muscle control, mental retardation and a tendency to self mutilation

58
Q

What is the pyrimidine salvage pathway for uracil?

A

Uracil -> uridine with uridine phosphorylase then uridine -> UMP with kinase then UMP -> UDP -> UTP

59
Q

What is the pyrimidine salvage pathway for thymine?

A

Thymine -> deoxythymidine using thymidine phosphorylase then deoxythymidine -> dTMP using thymidine kinase then dTMP -> dTDP -> dTTP

60
Q

What is the role of Acyclovir?

A

An antiviral agent that resembles guanine and undergoes phosphorylation by viral thymidine kinase at a rate that exceeds cellular thymidine, converting acyclovir to acycloGMP and terminating replication

Danielle- MCM Test 1 (12 decks)

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