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Biochem III > Nucleotide Metabolism > Flashcards

Nucleotide Metabolism Flashcards

1
Q

What is a nucleoside?

A

base linked to 1’ of ribose

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2
Q

What is a nucleotide?

A

nucleoside esterified to a phosphate at 5’ of ribose ring

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3
Q

What two components are fused to make a pyrimidine?

A

purine and imidazole ring

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4
Q

Where are the enzymes for purine synthesis located?

A

cytoplasm

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5
Q

At what base is purine synthesis initiated?

A

PRPP

5-phosphoribosyl-1-pyrophosphate

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6
Q

What is the first step in purine synthesis? What enzyme catalyzes this reaction?

A

generation of PRPP

PRPP Synthetase

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7
Q

Is PRPP synthesis specific to purine synthesis?

A

No.

PRPP is required for both purine and pyrimidine synthesis

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8
Q

What is PRPP derived from?

A

ribose-5-phosphate

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9
Q

What is the committed step of de novo purine synthesis? What enzyme catalyzes this reaction?

A

formation of 5-phosphoribosylamine (5-PRA)

enzyme = amidophosphoribosyltransferase

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10
Q

What is the first purine to be produced during de novo synthesis?

A

inosine-5-monophosphate

IMP

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11
Q

IMP serves as a precursor for what two other purines?

A

AMP and GMP

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12
Q

What donate carbon and nitrogen atoms to purine synthesis?

A

amino acids

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13
Q

Specifically, what amino acids donate carbon and nitrogen to purine synthesis?

A

glycine, glutamine and aspartate

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14
Q

What does CO2 provide in purine synthesis?

A

carbon and oxygen

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15
Q

What does N10-formyl-THF provide in purine synthesis?

A

donor of one-carbon

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16
Q

What are the roles of nucleoside monophosphate kinases and nucleoside diphosphate kinases?

A

generation of nucleotide triphosphates

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17
Q

Which, NMPK orNDPK have a more specific or more general substrate specificity?

A

NMPK = more specific

NDPK = more broad

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18
Q

Why is GTP an ‘ATP Equivalent’?

A

the more are readily interconverted

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19
Q

What are the most effective inhibitors of PRPP Synthetase?

A

ADP and GDP

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20
Q

What serves to inhibit amidophosphoribosyltransferase activity?

A

AMP and GMP

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21
Q

What serves as an allosteric activator of amidophosphoribosyltransferase?

A

PRPP

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22
Q

Where does the bulk of purine nucleotide degradation occur?

A

the liver

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23
Q

How is the degrdation of GMP initiated?

A

5’-nucleotidases

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24
Q

What is the 2nd step of guanosine degradation? What two molecules are liberated?

A

purine nucleoside phosphorylase

guanosine –> guanine and ribose

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25
Q

How does AMP degradation begin?

A

by the action of AMP deaminase and adenosine deaminase

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26
Q

What does the action of AMP deaminase produce?

A

IMP from AMP

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27
Q

What enzyme converts AMP to adenosine?

A

5’-nucleotidases

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28
Q

What enzyme converts AMP to IMP?

A

AMP deaminase

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29
Q

What enzyme converts adenosine to inosine?

A

adenosine deaminase

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30
Q

What enzyme converts IMP to inosine?

A

5’-nucleotidases

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31
Q

What enzyme converts inosine to hypoxanthine?

A

purine nucleoside phosphorylase

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32
Q

What enzyme converts hypoxanthine to xanthine?

A

xanthine oxidase

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33
Q

What enzyme converts GMP to guanosine?

A

5’nucleosidases

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34
Q

What enzyme converts guanosine to guanine?

A

purine nucleoside phosphorylase

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35
Q

What enzyme converts guanine to xanthine?

A

guanine deaminase

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36
Q

What two conditions can lead to a decrease in uric acid secretion?

A

real insufficiency and metabolic acidosis

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37
Q

What two conditions can cause an increase in nucleotide turnover that can exacerbate gout?

A

increased nucleotide turnover

diets rich in purine

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38
Q

How does alcohol consumption exacerbate gout?

A

alcohol consumption causes ATP turnover and increase in serum lactic acid

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39
Q

What are gout crystals?

A

sodium urate

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40
Q

What is it called when gout precipitates in the kidney?

A

uric acid urolithiasis

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41
Q

What is allopurinol oxidized to?

A

oxypurinol

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42
Q

How does oxypurinol aid in the treatment of gout?

A

oxypurinol is a competitive inhibitor of xanthine oxidase

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43
Q

How does pyrimidine synthesis differ from that of purine synthesis?

A

pyrimidines are synthesized as bases then attached to ribose

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44
Q

What is the first enzyme of pyrimidine synthesis?

A

Carbamoyl Phosphate Synthetase II

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45
Q

What is the product of carbamoyl synthetase II?

A

carbamoyl phosphate

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46
Q

What enzyme acts on carbamoyl phosphate? What does this produce?

A

Aspartate Transcarbamoylase

N-carbamoyl aspartate

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47
Q

What enzyme works on N-carbamoyl aspartate?

A

Dihydroorotase

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48
Q

What does dihydroorotase produce?

A

dihydroorotate

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49
Q

What enzyme of pyrimidine synthesis is expressed in the mitochondria?

A

Dihydroorotate Dehydrogenase

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50
Q

What does dihydroorotate dehydrogenase work on? What does dihydroorotase produce?

A

dihydroorotate

orotate

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51
Q

What enzyme works on orotate? What is the product of this enzyme?

A

orotate phosphoribosyl transferase

OMP

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52
Q

What enzyme works on OMP? What is the product of this enzyme?

A

OMP decarboxylase

UMP

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53
Q

What enzyme catalyzes the transfer of R5P to orotate?

A

orotate phosphoribosyltransferase

54
Q

What is OMP also known as?

A

orotidine 5 monophosphate

55
Q

What is CAD?

A

carbamoyl phosphate synthetase, aspartate transcarbamoylase, dihydroorotase

56
Q

What two enzymes make up UMP synthase?

A

OMP decarboxylase and orotate phosphoribosyl transferase

57
Q

Orotic aciduria features a defect in what enzyme?

A

UMP synthase

58
Q

What three symptoms do patients with orotic aciduria present with?

A

orotic acid in urine

megaloblastic anemia

occasional defect in cellular immunity

59
Q

What is the treatment for orotic aciduria?

A

pyrimidine supplementation

60
Q

What does CTP synthase use as an amino donor?

A

glutamine

61
Q

Where is de novo synthesis of pyrimidines most regulated?

A

carbamoyl phosphate synthetase II

62
Q

Regarding CTP synthase, what kind of effector is CTP?

A

negative effector

63
Q

What kind of kinetics does CTP synthase display regarding UTP levels?

A

sigmoidal kinetics

64
Q

Activity of carbamoyl phosphate synthetase II is affected by what two molecules?

A

inhibited by UTP

activated by PRPP

65
Q

What enzyme produces deoxyribonucleotides?

A

ribonucleotide reductase

66
Q

What is the substrate for ribonucleotide reductase?

A

nucleoside 5’ Di-phosphates

67
Q

What is the product of ribonucleotide reductase?

A

2’-deoxyribonucleotide -5’-diphosphates

68
Q

How are ribonucleotide reductase levels regulated?

A

transcription

69
Q

What is a common and important pharmacological inhibitor of ribonucleotide reductase?

A

hydroxyurea

70
Q

Mutations in adenosine deaminase are implicated in what disease?

A

severe combined immunodeficiency disease

71
Q

Why is adenosine deaminase believed to cause SCID?

A

back-up of adenosine metabolites inhibits ribonucleotide reductase

72
Q

How is dTMP converted to dTDP?

A

dTMP kinase

73
Q

What is the classic inhibitor of thymidylate synthase?

A

5-fluorouracil

74
Q

In the body, what is 5-FU converted to?

A

fUMP

75
Q

What form of 5-fluorouracil is a substrate for ribonucleotide reductase?

A

fUDP

76
Q

Dephosphorylation of what producs fdUMP?

A

fdUDP

77
Q

Specifically, how does 5-FU inhibit thymidylate synthase?

A

FdUMP and N5N10 THF form a permanent and irreversible complex with thymidylate synthase

78
Q

Degradation of pyrimidines yield what two products?

A

beta-alanine

beta-aminoisobutyrate

79
Q

Where are nucleosides taken up?

A

intestinal epithelial cells

80
Q

Why is adenosine interesting?

A

adenosine can be directly phosphorylated by adenosine kinase to produce AMP

81
Q

What does Lesch-Nyhan Syndrome result from?

A

defective HGPRTase

82
Q

How do salvage pathways decrease de novo synthesis?

A

By sequestering PRPP and lowering activity of amidophosphoribosyl transferase

83
Q

What is the one pyrimidine that is not salvaged in humans?

A

cytosine

84
Q

What enzyme do fungi express that make them susceptible to analogs?

A

cytosine deaminase

85
Q

How does probenecid work?

A

inhibits renal uptake of uric acid

86
Q

What enzyme in pyrimidine synthesis uses PRPP?

A

orotate phosphoribosyltransferase

87
Q

What disease is UMP synthase defective in?

A

orotic aciduria

88
Q

How is orotic aciduria treated?

A

uridine administration

89
Q

What does CTP synthase use as a nitrogen source?

A

glutamine

90
Q

What is CPS II inhibited by?

A

UTP

91
Q

What is CPS II activated by?

A

PRPP

92
Q

What is CTP synthase inhibited by?

A

CTP

93
Q

What is CTP synthase activated by?

A

UTP

94
Q

What is an important inhibitor of ribonucleotide reductase?

A

hydroxyurea

95
Q

What does ribonucleotide reductase work on?

A

5’-nucleoside diphosphates

96
Q

What enzyme is deficient in patients with SCID?

A

adenosine deaminase

97
Q

What kind, oxy or deoxy, form of thymine exists?

A

Only deoxy

98
Q

What is another inhibitor of thymidylate synthase?

A

methotrexate

99
Q

How does methotrexate inhibit thymidylate synthase?

A

inhibitor of dihydrofolate reductase

100
Q

What is beta-alanine metabolized into?

A

acetyl-CoA

101
Q

What is dTMP metabolized into?

A

beta-aminoisobutyrate

102
Q

What is the function of adenosine kinase?

A

to phosphorylate adenosine to AMP

103
Q

What is the pyrimidine that IS NOT salvaged in humans?

A

cytosine

104
Q

What do fungi express that make them vulnerable to 5-fluorocytosine?

A

cytosine deaminase

105
Q

What does cytosine deaminase synthesize from 5-fluorouracil?

A

FUMP

106
Q

What structures provide carbon and nitrogen for IMP synthesis?

A

glycine, glutamine and aspartate

107
Q

What form of THF is used for purine synthesis?

A

N10-formyl-THF

108
Q

What is the ATP consumption required to synthesize the first purine, IMP?

A

four ATPs consumed

109
Q

What is the rate limiting step of AMP synthesis?

A

adenylosuccinate synthetase

110
Q

What it the rate limiting step of IMP synthesis?

A

IMP dehydrogenase

111
Q

What is amidophosphoribosyltransferase inhibited by?

A

AMP and GMP

112
Q

What is PRPP synthetase inhibited by?

A

ADP and GDP

113
Q

What serves as an allosteric activator of amidophosphoribosyltransferase?

A

PRPP

114
Q

What is the function of AMP deaminase?

A

AMP –> IMP

115
Q

What is the function of adenosine deaminase?

A

adenosine –> Inosine

116
Q

What is more common, reduced excretion of uric acid or increased production of uric acid?

A

reduced excretion

117
Q

How does alcohol contribute to gout?

A

increases serum lactic acid

uric acid competes with other organic acids for excretion

118
Q

What enzyme converts dUMP to dTMP?

A

thymidylate synthase

119
Q

What products get degraded to beta-alanine?

A

dCMP, CMP, UMP, uracil

120
Q

What products get degraded to beta-aminoisobutyrate?

A

dTMP, thymine

121
Q

Pyrimidine degradation requires what reducing agent?

A

NADPH

122
Q

How are beta-alanine and beta-isobutyrate excreted?

A

urine

123
Q

What is the function of adenosine kinase?

A

Adenosine –> AMP

124
Q

What enzyme is deficient in Lesch-Nyhan Syndrome?

A

HGPRTase

125
Q

What enzyme is responsible for pyrimidine salvage?

A

Pyrimidine Phosphoribosyltransferase

126
Q

What is the one pyrimidine that is not salvaged in humans?

A

cytosine

127
Q

How are the activities of HGPRTase and APRTase regulated?

A

the activity is inhibited by their products (IMP, GMP, AMP)

128
Q

What is beta-alanine metabolized to?

A

acetyl-CoA

129
Q

What is beta-aminoisobutyrate metabolized into?

A

succinyl-CoA

130
Q

What metabolite of pyrimidine degradation is unique to pyrimdine degradation?

A

beta-aminoisobutyrate

Biochem III (9 decks)

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