Module 7 Flashcards

1
Q

Monomeric units that make the nucleic acids DNA and RNA

A

Nucleotides

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2
Q

Responsible for the storage and passage of theinformation needed for the productions of proteins?

A

Nucleic acids

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3
Q

Each nucleotides consists of?

A

Pentose sugar,
Nitrogenous base
Phosphate group

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4
Q

Nucleotides result from linking one or more phosphates with a nucleoside onto the 5’ end of the molecule through

A

Esterfication

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5
Q

5-carbon sugar in a pentose ring form

A

Pentose sugar

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6
Q

RNA contains ribose, which has a hydroxyl group in both the

A

2 and 3 position

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7
Q

DNA has only a single hydroxyl group in the

A

3 position

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8
Q

Lacks a 2’-OH group

A

2 deoxyribose

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9
Q

Bond between adenine and deoxyribose

A

Glycosidic bond

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10
Q

Nucleosides

A

dAdenosine

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11
Q

Nucleotides

A

dAdenylic acid ( dAMP)

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12
Q

A nitrogenous base is attached by a glycosidic bond to the __________of the nucleotide’s sugar

A

1 carbon

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13
Q

Purinesconsist of linked 5-membered and 6membered rings__________ and _________) which can be found in DNA or RNA

A

Adenine A
Guanine G

5 and 6 membered rings

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14
Q

Pyrimidines consist of 6-membered rings

A

Cytosine C
Thymine T
Uracil U

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15
Q

Found in DNA and RNA

A

Cytosine

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16
Q

Found in DNA

A

Thymine

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17
Q

Found in RNA

A

Uracil

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18
Q

Nitrogenous base are

A

Planar, aromatic, and heterocyclic

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19
Q

Nitrogenous base derived from

A

Purine and pyrimidines

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20
Q

Nitrogenous base numbering of bases are

A

Unprimed

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21
Q

The sugar is linked to the base via a ___________ bond to the __________________

A

b-Nglycosidic bond
N-1 of pyrimidines
N-9 of purines

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22
Q

Purine nucleosides end in

A

Sine

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23
Q

Pyrimidine nucleosides end in

A

Dine

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24
Q

Nucleotides are linked together by ________________ between the _________ on the sugar of one nucleotide through a phosphate molecule to the ____________ on the sugar of another nucleotide

A

Phosphodiesterase bonds
3 hydroxyl
5 hydoxyl

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25
Q

Bondsof nucleotides are broken by?

A

Phosphodiesterase

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26
Q

Bond between complementary nucleotide chain and normal nucleotide chain.

A

Hydrogen bond

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27
Q

a second messenger in response to nitric oxide during smooth muscle relaxation

A

cAMPand cGMP

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28
Q

Function of nucleodtides

A

Syhtesis of cyclic AMP and GMP
Methyl group transfer
Glycogen, bilirubin, phosphoglyceride synthesis

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29
Q

Nucleotides absorb

A

UV lights

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30
Q

used as antivirals and in cancer chemotherapy

A

Synthetic nucleotide

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31
Q

targets for cancer chemotherapy and viral disease treatment

A

Purine and pyrimidine synthesis

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32
Q

activated precursors in nucleic acid synthesis

A

Nucleoside triphosphate

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33
Q

purines are not initially synthesized as free bases–First purine derivative formed is

A

Inosine monophophate

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34
Q

AMP and GMP are formed from

A

IMP or inosine monophosphate

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35
Q

The activated sugar used is 5-phosphoribosyl-1pyrophosphate, PRPP

A

Inosine monophosphate

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36
Q

PRPP is generated by the action of PRPP synthetase and requires energy in the form of

A

ATP

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37
Q

IMP is inhibited by

A

ADP and GDP (Allosteric

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38
Q

First committed step of purine synthesis

A

IMP

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39
Q

The major site of purine synthesis is in the

A

Liver

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40
Q

Synthesis of the purine nucleotides begins with ____________ and leads to the first fully formed nucleotide, ________________

A

PRPP

Inosine 5 moniphosphate

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41
Q

Synthesis of IMP requires

A
5ATP
2glutamine
1glycine
1Co2
1aspartate
2formate
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42
Q

The pathway leading to AMP requires energy in the form of

A

GTP

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43
Q

leading to GMP requires energy in the form of

A

ATP

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44
Q

Important enzyme and product in synthesis of AMP

A

Adenylosucinate lyase

Fumarate

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45
Q

Important enzyme and product in synthesis of GMP

A

GMP syhthetase

Glutamine and glutamate

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46
Q

The utilization of GTP in the pathway to AMP synthesis allows the cell to control the proportions of AMP and GMP to near ____________

A

Equivalence

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47
Q

Increase GTP

A

increase AMP

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48
Q

The synthesis of PRPP by PRPP synthetase is feed-back inhibited by

A

Purine 5 nucleotides

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49
Q

The essential rate limiting steps in purine biosynthesis occur at the

A

First two step of the pathway
PRPP synthetase
Amino transferase reaction

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50
Q

The amidotransferase reaction (2ndstep) catalyzed by PRPP glutamyl amidotransferase is also feed-back inhibited allosterically by

A

binding ATP, ADP and AMP at one inhibitory site and GTP, GDP and GMP at another

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51
Q

Increase ATP

A

Increase GMP

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52
Q

Increase AMP

A

Increase GMP

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53
Q

Increase GMP

A

Increase AMP

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54
Q

GTP AMP

A

Adenylosuccinate

55
Q

ATP GMP

A

Xanthylic acid

56
Q

Catabolism of the purine nucleotides leads ultimately to the production of ___________ which is insoluble and is excreted in the urine as __________

A

Uric acid

Sodium urate crystals

57
Q

The synthesis of nucleotides from the purine bases and purine nucleosides takes place in a series of steps known as the

A

Salvage pathway

58
Q

The free purine bases, adenine, guanine, and hypoxanthine, can be reconverted to their corresponding nucleotides by

A

Phosphoribosylation

59
Q

Two key transferase enzymes are involved in the salvage of purines

A

Adenosine phophoriboyltransferase

hypoxanthine-guanine phosphoribosyltransferase

60
Q

A critically important enzyme of purine salvage in rapidly dividing cells is ___________ (ADA) which catalyzes the deamination of adenosine to inosine

A

Adenosine deaminase

61
Q

Deficiency in ADA results in the disorder called

A

Severe combined immunodeficiency

62
Q

can also contribute to the salvage of the bases through a reversal of the catabolism pathways. However, this pathway is less significant than those catalyzed by the phosphoribosyltransferases

A

Purine nucleotide phosphorylases

63
Q

The synthesis of AMP from IMP and the salvage of IMP via AMP catabolism have the net effect of deaminating aspartate to

A

Fumarate

64
Q

Catabolism of purine nucleotide

A

purine nucleotide cycle

65
Q

the muscle-specific isoenzyme of AMP deaminase, and deficiencies in myoadenylate deaminase lead to post-exercise fatigue, cramping and myalgias

A

Myoadenylate deaminase

66
Q

Clinical problems associated with nucleotide metabolism in humans are predominantly the result of

A

Abnormal catabolism of purine

67
Q

Most forms of gout are the result of _______________ or to a partial deficiency in the salvage enzyme, __________

A

Excess purine production

HGPRT

68
Q

Responsible for re-forming IMP and GMP from hypoxanthine and guanine

A

HGPRT and the salvage system

69
Q

Most forms of gout can be treated by administering the antimetabolite

A

Allopurinol

70
Q

Allopurinol structural analog of hypoxanthine that strongly inhibits

A

Xanthine oxidase

71
Q

condition that results from the precipitation of urate (uric acid) as monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPPD) crystals in the synovial fluid of the joints, leading to severe inflammation and arthritis

A

Gout

72
Q

syndrome results from the loss of a functional HGPRT gene

A

Lesch nyhan syndrome

73
Q

The disorder is inherited as a sex-linked trait, with the HGPRT gene on the

A

X chromosome q 26-27

74
Q

Patients with this defect exhibit not only severe symptoms of gout but also a severe malfunction of the nervous system. •In the most serious cases, patients resort to selfmutilation. •Death usually occurs before patients reach their

A

20th year

75
Q

most often (90%) caused by a deficiency in the enzyme adenosine deaminase (ADA

A

SCID

76
Q

ADA deficiency selectively leads to a destruction of ________________, the cells that mount immune responses

A

B and T lymphocytes

77
Q

In the absence of ADA, ______________ is phosphorylated to yield levels of dATP that are 50-fold higher than normal

A

Deoxyadenosine

78
Q

The net effect of SCID is to inhibit __________ synthesis

A

DNA

79
Q

Since lymphocytes must be able to proliferate dramatically in response to antigenic challenge, the inability to synthesize DNA seriously impairs the immune responses, and the disease is usually fatal in infancy unless special protective measures are taken

A

Nice to know

80
Q

A less severe immunodeficiency results when there is a lack of __________________ another purinedegradative enzyme

A

Purine nucleoside phophorylase PNP

81
Q

Glycogen storage disease that also lead to excessive uric acid production

A

Von gierke disease

82
Q

Von gierke results from a dificiency in

A

Glucose 6 phosphatase

83
Q

The increased availability of glucose-6phosphate increases the rate of flux through the pentose phosphate pathway, yielding an elevation in the level of ribose-5-phosphate and consequently PRPP

A

Nice to know

84
Q

Pyrimidine Nucleotide Biosynthesis

A

1 glutamine
1 ATP
1 CO2
1 aspartate

85
Q

carbamoyl phosphate used for pyrimidine nucleotide synthesis is derived from

A

Glutamine and bicarbonate within the cytosol

86
Q

urea cycle carbamoyl phosphate derived from

A

Ammonia and bicarbonate within the mitochondrion

87
Q

Urea cycle: pyrimidine

A

CPS 1; CPS 2

88
Q

Carbamoyl phosphate is then condensed with aspartate in a reaction catalyzed by the rate limiting enzyme of pyrimidine nucleotide biosynthesis

A

Aspartate transcarbamoylase

89
Q

UMP Synthesis Overview •2 ATPs needed: both used in first step

A

Transfer phosphate

Hydrolyzed ADP and Pi

90
Q

UMP syhtesis 2 condensation reactions

A

Carbamoyl aspartate

OMP

91
Q

Pyrimidine ring syhtesize from

A

Carbomyl phosphate and aspartate

92
Q

Purine/Pyrimidine degradation are the same for ribonucleotides and deoxyribonucleotides •Biosynthetic pathways are only for ribonucleotide production •Deoxyribonucleotides are synthesized from corresponding ribonucleotides

A

Nice to know

93
Q

Ribose sugar in DNA lacks hydroxyl group at

A

2 carbon

94
Q

Reduction of 2’ carbon done via a free radical mechanism catalyzed by

A

Ribonucleotide reductase

95
Q

a multifunctional enzyme that contains redox-active thiol groups for the transfer of electrons during the reduction reactions

A

Ribonucleotide reductase

96
Q

RR is reduced in turn, by either

A

Thioredoxin or glutaredoxin

97
Q

The ultimate source of the electrons is

A

NADPH

98
Q

ATP ACTIVATES REDUCTION OF

A

CDP and UDP

99
Q

INHIBITS REDUCTION OF ALL NUCLEOTIDES

A

dATP

100
Q

STIMULATES ADP REDUCTION •INHIBITS CDP,UDP,GDP REDUCTION

A

dGTP

101
Q

INDUCES GDP REDUCTION •INHIBITS REDUCTION OF CDP. UDP

A

dTTP

102
Q

The dUMP is converted to dTMP by the action of

A

Thymidylate synthase

103
Q

The de novopathway to dTTP synthesis first requires the use of dUMP from the metabolism of either UDP or CDP

A

Nice to know

104
Q

The methyl group (recall that thymine is 5-methyl uracil) is donated by

A

N5 N10 methylene

105
Q

The unique property of the action of thymidylate synthase is that the THF is converted to _________________, the only such reaction yielding DHF from THF

A

Dihydrofolate

106
Q

In order for the thymidylate synthase reaction to continue, THF must be regenerated from DHF. This is accomplished through the action of

A

Dihydrofolate reductase

107
Q

THF is then converted to N5,N10-THF via the action of _________________

A

Serine hydroxymethyl transferase

108
Q

The crucial role of DHFR in thymidine nucleotide biosynthesis makes it an ideal target for chemotherapeutic agents such as ___________ and ____________, which are structural analogues of PABA and Folic acid

A

Sulfonamides

Trimethoprim

109
Q

cannot use exogenous folate but must synthesize it from PABA

A

Sulfonamide susceptible organisma

110
Q

also useful as an antibacterial; it does not affect mammalian cells because it is about 50,000 times less efficient in inhibition of mammalian dihydrofolate reductase

A

Trimethoprim

111
Q

used in cancer chemotherapy

A

Methotrexate

112
Q

The salvage pathway to dTTP synthesis involves the enzyme ___________ which can use either thymidine or deoxyuridine as substrate

A

Thymidine kinase

113
Q

Thymidine kinase is inhibited by

A

dTTP

114
Q

The regulation of pyrimidine synthesis occurs mainly at the first step which is ctalyzed by

A

Aspartate trabscarbamoylase, ATCase

115
Q

ATCase is inhibited by

A

CTP, UDP, UTP, and dUTP

116
Q

multifunctional protein in mammalian cells. It is capable of catalyzing the formation of carbamoyl phosphate, carbamoyl aspartate, and dihydroorotate

A

ATCase

117
Q

ATCase, and therefore the activity of CPSII, is localized to the __________ and prefers ___________ as a substrate

A

Cytoplasm

Glutamine

118
Q

The role of glycine in ATCase regulation is to act as a competitive inhibitor of the glutamine binding site

A

Glutamine binding site

119
Q

As in the regulation of purine synthesis, ATP levels also regulate pyrimidine biosynthesis at the level of

A

PRPP formation

120
Q

Catabolism of the pyrimidine nucleotides leads ultimately to __________(when CMP and UMP are degraded

A

Beta alanine

121
Q

when dTMP is degraded catabolism of nucleotides

A

Beta aminoisobutyrate

122
Q

The β-alanine and β-aminoisobutyrate serve as NH2 donors in transamination of

A

α-ketoglutarate to glutamate

123
Q

which can be diverted to fatty acid synthesis

A

Malonyl CoA

124
Q

which is converted to succinyl-CoA and can be shunted to the TCA cycle

A

Methylmalonyl CoA

125
Q

The salvage of pyrimidine bases has less clinical significance than that of the purines, owing to the solubility of the byproducts of pyrimidine catabolism

A

Nice to know

126
Q

Uracil can be salvaged to form UMP through the concerted action of

A

Uridine phisphorylase

Uridine kinase

127
Q

Formation of dTMP, by salvage of thymine requires

A

thymine phosphorylase and thymidine kinase

128
Q

The salvage of deoxycytidine is catalyzed by

A

deoxycytidine kinase

129
Q

Two inherited disorders affecting pyrimidine biosynthesis are the result of deficiencies in the bifunctional enzyme catalyzing the last two steps of UMP synthesis

A

orotate phosphoribosyl transferase and OMP decarboxylase

130
Q

causes retarded growth, and severe anemia caused by hypochromic erythrocytes and megaloblastic bone marrow

A

Orotic aciduria

131
Q

also common in orotic acidurias

A

Leukopenia

132
Q

can also cause orotic aciduria because it can act as an alternate substrate and compete with orotic acid for degradation

A

Allopurinol

133
Q

Orotic aciduria can be treated with

A

uridine and/or cytidine