Unit 7 Flashcards

1
Q

DNA and RNA purines

A

Adenine

Guanine

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2
Q

RNA pyrimidines

A

Cytosine

Uracil

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3
Q

DNA pyrimidines

A

Thymine

Cytosine

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4
Q

Difference between purines and pyrimidines

A

Purines have 2 rings

Pyrimidines have only 1

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5
Q

Nucleosides end will end in

A

-one

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6
Q

Nucleotides will end in:

A

-late

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7
Q

What can synthesize nucleotides in the de novo pathway?

A

Amino acids

Ribose-5-phosphate,

CO2

NH3

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8
Q

In the salvage pathway, nucleotides can be salvages from _______ released from the breakdown of:

A

Nucleobases

Nucleic acids

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9
Q

Compounds that inhibit ______ pathways are promising anti-parasite drugs

A

Salvage

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10
Q

In purine de novo biosynthesis, bases are synthesized while attached to:

A

Ribose

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11
Q

In pyrimidine de novo biosynthesis, only (BEFORE/AFTER) complete synthesis of bases, they are attached to what?

A

Before

Activated sugar 5-phosphoribosyl-1-pyrophosphate (PRPP)

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12
Q

Site of purine synthesis

A

Liver

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13
Q

Amino acids in purine ring

A

Glycine

Aspartate

Glutamine

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14
Q

Major contributors of purine ring

A

Amino acids

CO2

N10- formyl THFf

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15
Q

End products of de novo purine biosynthesis

A

Ribonucleotides

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16
Q

Activator or PRPP synthetase

A

Pi

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17
Q

Inhibitors of PRPP synthetase

A

Purine

Ribonucleotides

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18
Q

De novo biosynthesis of purines begins with:

A

PRPP with glutamine

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19
Q

During de novo biosynthesis of purines, what are synthesized as AMP and GMP?

A

Adenine and guanine

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20
Q

In de novo biosynthesis of purines, the ring builds up following the addition of:

A

3 atoms from glycine

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21
Q

What is the first intermediate with a full purine ring?

A

Inosin monophosphate (IMP) or inosinate

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22
Q

Intermediate needed for Inosinate to adenylosuccinate

A

Adenylosuccinate synthetase

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23
Q

What enzymes are needed for IMP - adenylosuccinate

A

Aspartate and GTP

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24
Q

Intermediate for IMP to XMP (xanthylate)

A

IMP dehydrogenase

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25
Q

Enzymes needed for IMP- XMP

A

H2O,

NAD+

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26
Q

To make GMP, inosinate is deoxidized to _______,

This then takes on intermediate ________, with enzymes ___ and ______ to GMP

A

Xanthylate

XMP-glutamamine aminotransferase

Glen
ATP

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27
Q

Site of nucleic acid degradation

A

Gut

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28
Q

In the stomach, what denatures nucleic acid?

A

Low pH

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29
Q

What hydrolysis nucleic acids to nucleotides?

A

Pancreatic nucleases

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30
Q

Intestinal mucosal cells derived nucleotides ________ nucleotides to nucleosides

A

Dephosphorylate

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31
Q

______ nucleosidases generate nitrogenous bases

A

Intestinal

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32
Q

Review slide 10 picture

A

Slide 10

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33
Q

Autosomal recessive deficiency that causes a type o f severe combined immunodeficiency (SCID), involving T cell, B cell and natural killer-cell depletion (lymphocytopenia)

A

Adenosine Deaminase (ADA) deficiency

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34
Q

In catabolism of purine, adenosine is deaminated to _______

Then hydrolysis to:

A

Inosine

Hypoxanthine and xanthine

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35
Q

In catabolism of purine, guanosine yields ______ via:

A

Xanthine

Hydrolysis and deamination

36
Q

In catabolism of purine, xanthine is oxidized into ______ by:

A

Uric acid

Xanthine oxidase

37
Q

What is a cofactor for xanthine oxidase?

A

Molybdenum

38
Q

Rare autosomal recessive deficiency that only affects T cells .

A

Purine nucleoside phosphorylase (PNP) deficiency

39
Q

Problems PNP deficient people have

A

Recurrent infections and neurodevelopment delay

40
Q

Disorder characterized by uricemia with recurrent attacks of acute arthritic joint inflammation, caused by deposition of mono-sodium irate crystals

A

Gout

41
Q

In gout, the hyperuricemia results primarily from :

A

The underexcretion of uric acid

42
Q

Treatment with ______ inhibits xanthine oxidase, resulting in an accumulation of:

A

Allopurinol

Hypoxanthine and xanthine (compounds more soluble that uric acid)

43
Q

What is important for both salvage and de novo synthesis

A

PRPP

44
Q

What is reused in salvage pathways for purines?

A

Free bases released in metabolism

45
Q

Adenine reacts with PRPP to form:

It is catalyzed by:

A

Adenine nucleotide AMP

Adenine phosphoribosyltransferase

46
Q

Organ especially dependent on salvage pathway

A

Brain

47
Q

Lack of hypoxanthine-guanine phosphoribosyltransferase leads to:

A

Lesch-Nyhan syndrome

48
Q

Syndrome that causes neurological impairment, and finger and toe biting behavior

A

Lesch-Nyhan syndrome

49
Q

Catalyst for hypoxanthine -> IMP

A

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

50
Q

Catalyst for guanine to GMP

A

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

51
Q

CPS I

Cellular location:

Pathway involved:

Source of nitrogen:

Regulators:

A

Mitochondria

Urea cycle

Ammonia

Activator: N-acetyl-glutamate

52
Q

CPS II

Cellular location:

Pathway involved:

Source of nitrogen:

Regulators:

A

Cytosol

Pyrimidine synthesis (de novo)

Gamma-amide group of glutamine

Activator: PRPP

Inhibitor: UTP

53
Q

What is the first full ring synthesized in de novo biosynthesis of pyrimidines?

A

Dihydroorotate

54
Q

Intermediate for Orotate -> Crotidine 5’monophosphate

A

Orotate phosphotibosyl transferase

Also takes in PRPP here

55
Q

Intermediate for Crotidine 5’-monophosphate ->.Uridine 5’-monophosphate

A

OMP decorboxylase

56
Q

First Nucleotide formed in de novo biosynthesis of pyrimidines

A

Uridine 5’-monophosphate

57
Q

Low activity of Orotate phosphoribosyltransferase and/or OMP decarboxylase could result in:

A

Poor growth,

Megoblastic anemia

Excretion of large amounts of Orotate in the urine

58
Q

What helps improve anemia and decreased excretion of Orotate?

A

Administration of uridine

59
Q

Ribonucleotides are precursors to:

A

Deoxyribonucleotides

60
Q

Activated state of ribonucleotide reductase is:

A

Deoxidized, with sulfa-hydro containing enzymes

61
Q

What enzymes are needed to oxidize ribonucleotide reductase?

What do they do?

A

Glutaredoxin or thioredoxin

Two H atoms are donated by NADPH and Carried by these two.

62
Q

Activator at primary regulatory sites for regulation of ribonucleotides

Inhibitor:

A

ATP

dATP

63
Q

Activator of substrate specificity for regulation of ribonucleotides

A

DATP,

Binding of substrates will activate one another

64
Q

Deamniation of ___ or phosphorylation of ____ yields dUTP

A

DCTP

dUDP

65
Q

Dephosphorylation of _____ by _____ yields dUMP

A

DUPT

DUTPase

66
Q

Methylation of dUMP by ______ ______ yields ___

A

Thymidylate synthase

DTMP

67
Q

What is a target for anti cancer drugs?

A

Thymidylate synthase

68
Q

DTMP is found exclusively found where?

A

In DNA

69
Q

DUDP -> dUTP needs what ?

A

Nucleoside diphosphate kinase

70
Q

DUMP -> DTMP need what?

A

Thymidylate synthase

71
Q

Cancer drugs will block ________ and/or ______

A

N5,N10-methylene-tetrahydrofolate

7,8 dihydrofolate

72
Q

_______ and _______ are important chemotherapeutic agents

A

Fluorouracil

Methotrexate

73
Q

In cells, fleorouracil is converted to _____, which inhibits _____ ____

A

FDUMP

Thymidylate synthase

74
Q

Methotrexate, a structural analog of ______, inhibits _____ ____

A

Tetrahydrofolate

Dihydrofolate reductase

75
Q

Widespread deficiency in nutritionally poor populations

A

Folic acid deficiency

76
Q

Folic acid deficiency leads to:

A

Reduced Thymidylate synthesis

77
Q

Reduced Thymidylate synthesis causes:

A

Uracil to be incorporated into DNA

78
Q

In catabolism and salvage of pyrimidines, the ring is:

A

Open

79
Q

Catabolism and salvage of pyrimidines-
CMP and UMP degrade to:

TMP degrades to:

Final end products:

A

Beta-alanine

Beta-aminosobutyrate

NH3/Urea and CO2

80
Q

Painful joints (often in toes) due to deposits of sodium urate crystals

A

Gout

81
Q

Does gout primarily effect males or females?

A

Males

82
Q

Gout may involve genetic under-excretion of ______, and/or over-consumption of _____

A

Urate

Fructose

83
Q

How is gout treated?

A

With avoidance of purine-rich foods (seafood, liver)
Or avoidance of fructose

Or with xanthine oxidase inhibitor allopurinol

84
Q

Allopurinal can also be used to treat:

Why?

A

Sleeping sickness (trypanosomiasis)

Trypanosomes lack enzymes for de novo nucleotide synthesis

85
Q

Trimethoprim can inhibit _____ ____ ____, but binds:

A

Bacterial Dihydrofolate

Human enzyme several orders of magnitude less strongly

86
Q

Principle electron reduction for ribonucleotide reductase

A

NADPH