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Hematology Exam 1 > Nucleotide Metabolism > Flashcards

Nucleotide Metabolism Flashcards

1
Q

TMP is formed from dUMP by addition of ____

A

5,10-methylene-FH4 (THF)

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2
Q

High inorganic phosphate levels indicates low _____ levels

A

nucleotide

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3
Q

What is a good treatment for hereditary orotic urinemia?

A
  • Uridine; Forms UTP (salvage pathway) that then goes to form CTP

** UTP also inhibits CSP II that then goes to reduce the levels of orotic acid that are formed de novo

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4
Q

Arts Syndrome is an x-linked genetic disorder in what enzyme?

A
  • PRPP synthetase
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5
Q

About what % of nucleotides come from the diet in humans?

A
  • 5%; most RNA and DNA in the diet are degraded and excreted
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6
Q

A deficiency in purine nucleoside phosphorylase causes what kind of immunodeficiency?

A

T-cell

** Nucleoside accumulate and the increase in dGTP and decrease in GMP may contribute to the symptoms and be toxic to lymphocytes

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7
Q

Leflunomide blocks orotate production in the ______ formation pathway

A

pyrimidine

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8
Q

CTP synthetase + glutamine takes UTP and forms ____

A

CTP

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9
Q

Pyrimethamine is used in the treatment of ____ and is derived from purines

A

Malaria

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10
Q

Gout occurs when there are [high/low] levels of uric acid in the blood

A

-high

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11
Q

If have a deficiency in adenosine deaminase (ADA), then what condition would you have?

A

SCID

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12
Q

When making purines de novo, what do you start with to make nucleotides?

A

Glucose

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13
Q

Folic acid = Vit ___

A

B9

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14
Q

In the guanosine (nucleoside) interconversion pathway, ribose 1-phosphate is lost and guanine (free base) is formed using what enzyme?

A
  • Purine nucleoside phosphorylase
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15
Q

In purine degradation, nucleic acids are turned into free bases and then into _____ that then turns into uric acid that is excreted in the urine

A

Xanthine

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16
Q

The inactive form of glutamine phosphoribosyl amidotransferase is a _____ and the active form is dimerized by the increase in ____ levels

A

Dimer; IMP, GMP, AMP

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17
Q

Methotrexate inhibits ____ and this drug is useful in the treatment of some cancers by slowing down DNA synthesis

A

DHFR

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18
Q

6- Mercaptopurine inhibits _____ synthesis

A

Purine

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19
Q

In over 90% of cases, gout is caused by an [overproduction/ underexcretion] of uric acid

A

Underexcretion

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20
Q

Aspartate + [Glutamine + CO2+ 2___]—> ____ _____ and this reaction uses the enzyme CPS-II

A

ATP; Carbamoyl phosphate

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21
Q

Increasing the levels of PRPP in some cases of gout leads to the increase activity of what rate-limiting enzyme?

A
  • Glutamine phosphoribosyl amidotransferase
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22
Q

Ribonucleotide reductase requires the cofactor _____ and NADPH from the pentose phosphate pathway to reduce NDP to dNDP

A
  • thioredoxin
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23
Q

Nucleotide salvage occurs mainly in the _____ and it is the process of buliding nucleotides from nucleosides and ____

A

Liver; bases

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24
Q

Trimethoprin (Septra) is used to treat _____ infections and is derived from ______

A

bacterial; purines

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25
Q

Where in the body is uric acid generated and then transported?

A

Liver and then to the kidneys

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26
Q

Position 1 (nitrogen) of nucleotides comes from ______

A

Aspartate

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27
Q

IMP forms _______ and then AMP. What is the energy source and the amino acid needed to form this intermediate?

A

Adenylosuccinate; GTP and aspartate

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28
Q

Hyperuricemia leads to what condition?

A

Gout

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29
Q

___ in the stomach degrades nucleic acids and ____ from the pancreas breaks the nucleotides down even more

A

Pepsin, nucleases

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30
Q

When adding a phosphate to ADP, GDP and others NDPs, what enzyme is needed and is it specific to the nucleosides?

A

Nucleoside diphosphate kinase; No

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31
Q

Allopurinol is used in the treatment of ____ and is derived from purines

A

Gout

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32
Q

Carbons 4,5 and nitrogen at 7 comes from ____ to build purines

A

Glycine

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33
Q

5-Fluorouracil is an anti-tumor drug that inhibits the enzyme thymidylate synthase that inihibits the conversion of dUMP to _____

A

dTMP

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34
Q

The salvage pathway is very _____ favorable

A

Energetically

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35
Q

Allopurinol is converted to ______ and that form is an irreversible inhibitor of ____ _____

A

oxypurinol; xanthine oxidase

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36
Q

von Gierke disease is a disease that is caused by a genetic deficiency in _______ that leads to glucose-6-phosphate being shunted into the pentose phosphate pathway that leads to production of __________ which eventually leads to hyperuricemia

A
  • glucose 6-phosphatase; ribose 5-phosphate
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37
Q

Folate is converted to _____ by DHFR and requires NADPH and then converted to ______ by DHFR and requires NADPH and then a formyl group is added to the ___ position

A

Dihydrofolate; Tetrahydrofolate; 10th

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38
Q

Carbomoyl phosphate + _____ = Carbamoyl aspartate –> _____

A

asparate; orotic acid

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39
Q

Mutations in UMP synthase cause what hereditary disease that results in poor growth, anemia, and high levels of orotic acid in the urine?

A

-Hereditary orotic aciduria

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40
Q

IMP is converted to XMP and then ___ by what enzyme?

A

GMP; IMP dehydrogenase

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41
Q

Monosodium urate crystals in the _____ results in inflammatory response

A

joints

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42
Q

Hydroxyurea is used to treat leukemia and sickle cell anemia. Which enzyme does it inhibit and what does this cause?

A

Ribonucleotide reductase; causes reduced DNA synthesis due to the reduction in dNDPs

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43
Q

B-aminoisobutyrate and B-alanine are excreted in urine or converted to methylmalonyl-coA or malonyl-coA that are used in ____ ____ biosynthesis

A

fatty acid

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44
Q

Negative regulation of 5-phosphoribosyl 1- amine is even more inhibited when AMP is paired with ___ or ___ because there are two different regulatory sites and the combination is additive

A

IMP; GMP

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45
Q

Mecaptopurine is used to treat _____

A

Cancer

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46
Q

In pyrimidine degradation, cytosine is degraded to ____ and then that is degraded to B-alanine which is soluble

A

uracil

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47
Q

Positions 3 and 9 (nitrogens) of pyrimidines (and 3 of purines) comes from _____

A

Glutamine

48
Q

IMP forms GTP by first forming the intermediate XMP. What is the energy source and the amino acid needed to form GTP from XMP?

A

ATP; Glutamine

49
Q

When adding a phosphate to AMP and GMP, what type of enzymes are needed and are they specific to the nucleosides?

A

Kinase; yes

50
Q

Ribose-5-phosphate + ATP is converted to _____ with what enzyme?

A

PRPP; PRPP synthetase

51
Q

What is the goal of purine de novo synthesis?

A

To create ATP and GTP

52
Q

Deficiency in ADA results in accumulation of ____ and high levels of this is toxic to lymphocytes

A

dATP

53
Q

What enzyme converts ADP to dADP?

A

RR (ribonucleotide reductase)

54
Q

In DNA, what constituent is at the 2’ carbon?

A

-H

55
Q

What is necessary to combine with the free bases (adenine, hypoxanthine, guanine) in the purine salvage pathway to create nucleotides?

A
  • PPRT
56
Q

Mycophenolic acid inhibits what enzyme resulting in its property of immunosuppression?

A

IMP dehydrogenase

57
Q

List the pyrimidines:

A
  1. Cytosine
  2. Uracil
  3. Thymine

** CUT the PY (pie)

58
Q

Negative regulation of 5-phosphoribosyl 1- amine is very sensitive to levels of ____ because the Km is much lower showing a sigmoidal curve

A

PRPP

59
Q

How many ways are there to produce dUMP?

A

2

60
Q

THF carries __ carbon and that is added to the __ and ___ position on nucleotides (purines)

A

1 carbon; 2nd and 8th position

61
Q

Nucleoside is a base + ____

A

sugar

62
Q

In the purine salvage pathway, adenine is converted into AMP using what enzyme?

A

APRT

63
Q

Orotic acid (Orotate) + ____ –> OMP –> UMP; all of these reactions are catalyzed by UMP synthase

A

PRPP

64
Q

___ is much less stable than DNA

A

RNA

65
Q

THF donates how many carbons to purine biosynthesis?

A

-2 carobons at position 2 and 8

66
Q

What is the goal of pyrimidine de nove synthesis?

A

To create CTP, UTP, and TTP

67
Q

Why would some cancer patients be treated with allopurinol or rasburicase?

A

Because during tumor cell lysis (via treatment with chem and cytotoxic drugs), nucleic acids are being released and they are being degraded and converted to uric acid, thus leading to hyperuricemia

68
Q

If ___ is high then GMP/GTP is increased in the purine biosynthesis pathway

A

ATP

69
Q

Nucleotide is a base + sugar + ____

A

Phosphate groups (mono, di, tri)

70
Q

If ___ is high then AMP/ATP is increased in the purine biosynthesis pathway

A

GTP

71
Q

Sequence of bulding purines

A
  1. Glycine (+ATP)
  2. THF (C2)
  3. Glutamine (+2ATP)
  4. CO2 (C6)
  5. Aspartate (+ATP)
  6. THF (C8)

** GTGCAT; “Got To Go CAT”

72
Q

PRPP + glutamine forms ____________ with the use of what enzyme?

A

5-phosphoribosyl 1-amine; glutamine phosphoribosyl amidotransferase

73
Q

AMP is converted to adenosine and then adenosine is converted to inosine. What enzyme converts adenosine to inosine?

A
  • Adenosine deaminase
74
Q

PRPP + ____ = nucleotide

** Catalyzed by either HGPRT (hypoxanthine and guanine) or APRT (adenine)

A

Base

75
Q

What enzyme regulates the key step in pyrimidine biosynthesis?

A

CPS II

76
Q

Uric acid overproduction may occur when which enzymes is increased that leads to incrased PRPP levels?

A
  • PRPP synthetase
77
Q

Allopurinol inhibits ____ oxidase and is a treatment for gout

A

xanthine

78
Q

How does probenecid treat gout?

A
  • By increasing the excretion of uric acid
79
Q

Tetrahydrofolate is necesary to form dUMP. What drug inhibits dihydrofolate reductase?

A

Methotrexate

80
Q

Ribonucleotide reductase has 2 allosteric sites: one controls activity and the other controls _____ specificity

A

substrate

81
Q

Red blood cells and ______ use which pathway to create nucleotides?

A
  • Salvage
82
Q

High levels of dATP inhibits which enzyme that results in reduction in DNA synthesis

A

Ribonucleotide reductase (RR)

83
Q

NDP is converted to dNDP by which enzyme?

A

Ribonucleotide reductase (RR)

84
Q

Lesch Nyhan syndrome is an x-linked recessive disorder that causes a deficiency in HGPRT and that leads to increased levels of ____ and that drives which enzyme to make more 5-phosphoribosyl 1-amine leading to neurological problems and gout?

A
  • PRPP; glutamine phosphoribosyl amidotransferase
85
Q

In Arts Syndrome, there can be either a decrease or an increase in which enzyme?

A
  • PRPP synthetase
86
Q

In the pyrimidine salvage pathway, uracil or cytosine is converted to uridine or cytosine by adding ______. Thymine is converted to thymidine by adding ______.

A

Ribose 1-phosphate; Deoxyribose 1-phosphate

87
Q

Through which pathway is ribose- 5- phosphate made?

A
  • Pentose phosphate shunt
88
Q

The creation of 5-phosphoribosyl 1-amine is a ____ step and is irreversible in purine biosynthesis

A

committed

89
Q

AMP deaminase deficiency (AMP –> IMP) occurs in ____ and is often asymptomatic, but can lead to skeletal muscle myopathy and/or fatigue and cramps upon exercising

A

Muscle

90
Q

Thymine is degraded to ______ in pyrimidine degradation

A
  • B-aminoisobutyrate
91
Q

Pyrimidine nucleotide degradation products are _______ while purine nucleotide degradation products are _______

A

Soluble; insoluble

92
Q

Which organ is the primary producer of nucleotides?

A
  • Liver
93
Q

The active form of form of glutamine phosphoribosyl amidotransferase is a _______ and has increased activity with increased ____ levels

A

Monomer; PRPP

94
Q

Azidothymidine (AZT) is used to treat ____ and is derived from purines

A

HIV

95
Q

In forming pyrimidines, what occurs differently at the beginning?

A

Create the ring and then add the ribose and the phosphate

96
Q

Hypoxanthine is inosine + _______

A
  • ribose
97
Q

List the purines and derivatives

A

Purines:

  1. Adenine
  2. Guanine

Derivatives

  1. Xanthine
  2. Hypoxanthine
  3. Uric acid
98
Q

Inosine is a _______

A

nucleoside

99
Q

Acyclovir is used in the treatment of _____ and is derived from ______

A

herpes; purines

100
Q

Hypoxanthine is the base of ___

A

IMP

101
Q

Azathioprine (AZA) is derived from _____ and used in organ transplantation

A

Purines (A,G)

102
Q

Ribavirin is inhibits what IMP dehydrogenase and that inhibits ____ formation which makes it an effective anti-viral and anti-tumor drug

A

GMP

103
Q

In RNA, what constituent is at the 2’ carbon?

A

-OH

104
Q

Carbon 6 of purines and carbon 2 of pyrimidines comes from ___

A

CO2

105
Q

Allopurinol treats gout by doing what?

A

-Inhibiting xanthine oxidase, which decreases the production of xanthine from hypoxanthine that then goes to form uric acid

106
Q

Lesch-Nyhan Syndrome involves a deficiency in _______ that is a part of which pathway of purine biosynthesis?

A

HGPRT; salvage

107
Q

Rasburicase is a recombinant form of what enzyme that is present in animals that converts uric acid into a soluble allantoin?

A
  • Urate oxidase
108
Q

Sulfa antibiotics inhibit ____ folic acid synthesis

A

Bacterial

109
Q

In the purine salvage pathway, hypoxanthine and guanine are converted into IMP and GMP, respectively, using what enzyme?

A

HGPRT

110
Q
A
111
Q
A
112
Q
A
113
Q
A
114
Q
A
115
Q
A
116
Q
A
117
Q
A

Hematology Exam 1 (16 decks)

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