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GI > Nucleotide Metabolism II > Flashcards

Nucleotide Metabolism II Flashcards

1
Q

There is a key interaction between purine metabolism and the TCA cycle via

A

Fumarate

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2
Q

The interconversion of IMP to adenylosuccinate to AMP and then back to IMP with the release of fumarate

A

Purine nucleotide cycle

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3
Q

Any reaction that serves to replenish the intermediates of another metabolic process is called an

A

Anapleurotic reaction

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4
Q

In muscle cells, allows for increased energy production via the TCA cycle by replenishing supplies of fumarate

A

Purine nucleotide cycle

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5
Q

The parent base is synthesized in its entirety and then added to the PRPP backbone in

A

De novo pyridine synthesis

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6
Q

What is step 1, and also the regulated step, of pyrimidine synthesis?

A

Synthesis of Carbamoyl phosphate

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7
Q

Two molecules of ATP, 1 CO2, and glutamine are converted to carbamoyl phosphate by the enzyme

A

Carbamoyl synthase II (CPS-II)

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8
Q

The enzyme carbamoyl synthase II is activated by

A

ATP and PRPP

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9
Q

Carbamoyl synthetase II is inhibited by the eventual end product of its pathway, which is

-can then be converted to other pyrimidines

A

UTP

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10
Q

Note that carbamoyl phosphate is also synthesized in the

A

Urea cycle

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11
Q

However, in the urea cycle, the key enzyme involved is called

A

Carbamoyl synthetase I (CPS-I)

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12
Q

Located in the mitochondria

A

CPS-I

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13
Q

Located in the cytosol

A

CPS-II

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14
Q

Contributes only two of the atoms that comprise the six-membered pyrimidine ring

A

Carbamoyl phosphate

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15
Q

The remaining 4 atoms of the pyrimidine ring are supplied by

A

Aspartate

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16
Q

Carbamoyl phosphate synthetase and teo other enzymes are catalytic domains of one large polypeptide called

A

CAD

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17
Q

Serves to coordinated the synthesis of pyrimidines in both time and space, minimizing side reactions and ensuring greater efficiency

A

CAD

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18
Q

After one additional reaction that takes place on the outer face of the inner mitochondrial membrane, we end up with a ringed molecule called

A

Orotate

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19
Q

Once the pyrimidine base is formed, we attach it to the

A

Ribophosphate backbone

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20
Q

Orotate is attached to PRPP by the enzyme

A

Orotate Phosphoribosyl Transferase (OMP)

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21
Q

A precursor to the parent pyrimidine UMP

A

OMP

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22
Q

OMP is converted to Uridylate (UMP) by the enzyme

A

Orotidylate decarboxylase

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23
Q

Decreased activity of either orotate phosphoribosyl transferase or orotidylate decarboxylase results in a disease called

A

Orotic Aciduria

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24
Q

Characterized by megaloblastic anemia as well as large amounts of orotate in the urine

A

Orotic aciduria

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25
Q

Results from a deficiency of nucleotides in rapidly diviing marrow cells, leading to fewer, larger immature red cells

A

Megaloblastic anemia

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26
Q

Unlike most causes of megaloblastic anemia, is not corrected by supplementation with folate or vitamin B12

A

Orotic aciduria

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27
Q

We can treat orotic aciduria and bypass the metabolic block with supplementation of

A

CMP, UMP, or the base Uridine

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28
Q

UMP is phosphorylated by a nucleoside monophosphate kinase to produce

A

UDP

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29
Q

UDP is then further phosphorylated by nucleoside diphosphate kinase to form

A

UTP

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30
Q

The only way to synthesize cytosine nucleotides de novo is to

A

Convert UTP to CTP

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31
Q

The conversion of UTP to CTP requires the enzyme

A

CTP synthetase

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32
Q

The conversion of UTP to CTP by CTP synthetase requires

A

1 ATP and glutamine

33
Q

Serves to negatively inhibit CTP synthetase via a negative feedback mechanism

A

CTP

34
Q

Can be created from a precursor molecule called deoxyuridine monophosphate (dUMP)

A

Thymine

35
Q

Thymine can also be formed from the deamination of

A

Deoxycitidine monophosphate (dCMP)

36
Q

Required for DNA synthesis

A

Deoxyribonucleotides

37
Q

Deoxyribonucleotides are synthesized from ribonucleotides via the enzyme

A

Ribonucleotide Reductase

38
Q

Highly expressed in proliferating cells that enter the S-phase of the cell cycle

A

Ribonucleotide Reductase

39
Q

In order to catalyze the reaction, ribonucleotide reductase requires

A

NADPH

40
Q

Ribonucleotide reductase is inhibited by

A

dATP

41
Q

Ribonucleotide reductase is activated by

A

ATP

42
Q

Ribonucleotide reductase is inhibited by dATP, which prevents the enzyme from reducing

A

ADP, GDP, and UDP

43
Q

Determination of which substrate preferentially binds the enzymes catalytic site at any given time is regulated by the binding of the NTP to an auxillary site on the enzyme known as the

A

Substrate specificity site

44
Q

Binding of dATP is only inhibitory if it occupies to the

-not inhibitory when bound to the substrate specificity site

A

Active site

45
Q

Patients with ADA have high levels of

A

dATP

46
Q

This means that in ADA we see the inhibition of

A

Ribonucleotide reductase

47
Q

This blocks the production of all deoxyribonucleotides, which prevents the bone marrow from producing

A

B and T cells

48
Q

Synthesis of thymine nucleotides requires the molecule

A

dUMP

49
Q

dUMP is formed from the deamintion of

A

dCMP

50
Q

dUMP is also formed by the action of a phosphatase on

A

dUTP

51
Q

The main method of synthesizing dUMP

A

Deamination of dCMP

52
Q

Important in getting rid of excess dUTP to prevent it from getting incorporated into DNA

A

Phosphorylase activity on dUTP

53
Q

dUMP is ocnverted to thymidylate by the enzyme

A

Thymidylate synthase

54
Q

This reaction catalyzed by thymidylate synthase requires

A

N,N-methyleneTHF

55
Q

Covalently inhibits thymidylate synthase

A

The antitumor agent 5-fluorouracil

56
Q

To block thymidylate synthase, 5-fluorouracil is converted to

A

5-FdUMP

57
Q

Methotrexate and other inhibitors of DHFR prevents the recycling of THF, which blocks

A

Purine and TMP synthesis

58
Q

Requires 2 steps. The first step couples the base to a sugar and the second adds a phosphate to the nucleoside

A

Pyrimidine salvage

59
Q

In step 1, a pyrimidine base and ribose-1-phosphate are converted to a pyrimidine ribonucleoside and inorganic phosphate by

A

Nucleoside phosphorylase

60
Q

These phosphorylases can act on both

A

Ribose and deoxyribose substrates

61
Q

A pyrimidine nucleoside is phosphorylated to a pyrimidine nucleoside monophosphate by a

A

Nucleoside kinase

62
Q

Salvges the nucleoside thymidine to TMP

A

Thymidine kinase

63
Q

Interestingly, the herpes simplex virus encodes its own

A

Thymidine kinase

64
Q

This virus uses its own thymidine kinase to augment nucleotide supplies to promote its own replication

A

Herpes simplex virus

65
Q

A guanosine analog that interferes with viral replication

A

Acyclovir

66
Q

Gets phorphorylated by the viral thymidine kinase and gets preferentially incorporated into viral DNA, resulting in premature DNA chain termination

A

Acyclovir

67
Q

The catabolism of pyrimidines leads to

A

Highly soluble products

68
Q

CMP and UMP are degraded to

A

β-alanine

69
Q

TMP is degraded to

A

β-­‐aminoisobutyrate

70
Q

The degredation of pyrimidines results in the release of

A

Ammonia and CO2

71
Q

The single most important risk factor for developing gout

A

Serum Urate (SU)

72
Q

A sustained elevation of SU is essential to developing gout, but is it sufficient to cause the disease?

A

No

73
Q

Do the majority of patients with hyperuricemia develop gout?

A

No

74
Q

Uric acid crystalizes at a level of

A

6.8 mg/dL

75
Q

Abrupt and rapid onset causing severe pain. Often at night/early A.M.

A

Acute gout

76
Q

An inflammatory granuloma

A

The Tophus

77
Q

Deposits of monosodium urate crystals (MSU) crystals are surrounded by

A

Foreign body ganulomas

78
Q

All gout is

A

Tophaceous

GI (59 decks)

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