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Flashcards in Nucleotide Metabolism Deck (79):
1

Nucleotides functions

-structural component of DNA and RNA
-carriers of activated intermediates (UDP-glucose formation)
-secondary messengers in signal transduction (cAMP, cGMP)
-energy currency of the cell (ATP)
-regulators of many pathways

2

Nucleotide structural components of coenzymes

-CoA
-NAD+
-FAD
-NADP+

3

Main structural features of nucleotides

-Nitrogenous base
-sugar (can have phosphate associated)

4

Types of nitrogenous bases

-purines
-pyrimidines

5

Purines

-nitrogenous base
-adenine and guanine
-dicyclic

6

Pyrimidines

-nitrogenous base
-cytosine, thiamine (DNA), uracil (RNA
-unicyclic

7

Sugar of a nucleotide

-ribose in RNA
-deoxyribose in DNA (missing O)

8

What links the 2nd and 3rd phosphate on a nucleoside triphosphate (ATP)?

Anhydride bonds, high energy bonds driving many biochemical reactions
-this is why we can use them as energy source

9

Nucleoside

Nitrogenous base + sugar (no phosphate)

10

Nucleotide

-nucleoside + 1-3 phosphate groups

11

Where is the ribose 5-phosphate from in purine synthesis

HMP shunt

12

Purine synthesis

-dicyclic so they are bigger and more complicated
-we are essentially building base on a sugar molecule

13

Step 1 of purine nucleotide synthesis

-PRPP synthetase catalyzes the formation of the activated pentose

14

PRPP synthetase

-in step 1 of purine synthesis
-catalyzes the formation of the activates pentose

15

PRPP activator

Inorganic phosphate

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PRPP inhibitor

Purine ribonucleotides

17

Where is the pyrophosphate attached in purine synthesis?

1' carbon, which is where the nitrogenous base will be attached

18

PUrine nucleotide synthesis default

Production of ribonucleotides
-if deoxyribonucleotides are needed, further steps will be taken

19

Is the rate limiting step the first step of purine synthesis?

No

20

Rate limiting step of purine synthesis

-catalyze by PRPP amidotransferase
-committed step

21

After PRPP amidotransferase catalyzes purine synthesis...

The following steps are basically just modifying your base to get your purine
-amino acids become part of the nitrogenous bases

22

Folate

Required for purine synthsis, required for subsequent steps as a carbon donor

23

What form does folate need to be in to be activated?

THF

24

Dihydrofolate reductase

Required to make THF, the form in which folate is used
-have to have this enzyme to continue pathway.
-obtained from diet
-bacteria synthesize there own

25

PRPP amidotransferase inhibited by

Purine nucleotides (end products)

26

PRP amidotransferase reductase activated by

PRPP (substrate)

27

IMP can be utilized as...

AMP and GMP

28

What is the rate limiting and committed step in purine synthesis catalyzes by?

PRPP amidotransferase

29

6-Mercaptopurine

-purine analog
-acts like IMP, GMP, and AMP
-inhibits the PRPP amidotransferase
-cancer treatment
-can be misincorporated into the synthesis of purines and script the structure

30

What drug inhibits PRPP amidotransferase?

6-Mercaptopurine

31

Methotrexate

-folic acid analog
-anti-tumor
-inhibits dihydrofolate reductase

32

How does methotrexate affect dihydrofolate reductase?

-inhibits nucleotide biosynthesis
-inhibiting rapidly dividing cells selectively
-specific to mammalian cells

33

What is a drug that inhibits dihydrofolate reductase?

Methotrexate

34

Sulfonamides is the analog to...

PABA

35

What does sulfonamides do

Competitive inhibit of bacterial production of folic acid
-bacterial purine synthesis inhibited

36

What do sulfa drugs act as?

Antibiotics

37

What do sulfa drugs do in bacteria?

-binds to enzyme that produces folate, inhibits THF, can't produce purines

38

CPS II (Carbamoyl phosphate synthetase II)

-rate limiting, committed step in pyrimidine synthesis

39

What is the rate limiting, committed step in pyrimidine synthesis?

CPS II

40

What is CPS II activated by?

PRPP

41

What is CPS II inhibited by?

UTP (End product)

42

What two amino acids become part of the nitrogenous base structure of pyrimidines?

-glutamine
-aspartate

43

What provides the pentose for the pyrimidine?

PRPP

44

Once the pyrimidine bases are produced, what happens?

They are attached to PRPP

45

How do ribonucleotides get converted into deoxyribonucleotides?

Ribonucleotide reductase

46

Hydroxyurea

-anti tumor drug that inhibits ribonucleotide reductase

47

What drug inhibits ribonucleotide reductase?

Hydroxyurea

48

Hydroxyurea in sickle cell anemia treatment

-increases the synthesis of fetal hemoglobin

49

Thymidilate synthase

Plays a role in additional steps to convert dUMP into dTMP

50

What is thmidylate synthase inhibited by?

5-FU

51

What will affect the production of DNA, but not RNA?

Hydroxyurea and 5-FU
-are especially good at targeting rapidly dividing cells

52

What is required for thymidylate synthesis?

Folate, which then requires dihydrofolate reductase

53

What is dihydrofolate reductase inhibited by?

Methotrexate

54

Trimethoprim

Class of antibiotics that is selective for the prokaryotic version of dihydrofolate reductase

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Class of antibiotics that is selective for the prokaryotic version of dihydrofolate reductase

Trimethoprim

56

Sulfonamides

-antibiotics
-target enzymes in bacteria that make folic acid

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What are sulfonamides selectively;y toxic for?

Prokaryotes

58

What is the main mechanism of action of sulfonamides?

Inhibiting nucleotide metabolism in prokaryotes

59

Pyrimidine salvaging

-not salvaged to a significant degree
-no high yield diseases or enzymes are associated with their breakdown or salvage

60

Which bases are more complex?

Purine

61

Why are purines more complex than pyrimidines

-dicyclic
-many more steps involved
-salvage pathway is more critical

62

Salvage pathway for purines

-nitrogenous base is recovered after removing phosphate and sugar moieties
-yield hypoanthine or guanine which can be shuttled back into purine nucleotide synthesis

63

What does the salvage pathway for purines yield

-hypoxanthine or guanine

64

What happens to the hypoxanthine and guanine that is yielded from purine salvaging?

Shuttled back into purine nucleotide synthesis

65

Adenosine delaminase deficiency

Causes severe combined immunodeficiency disease (SCID)

66

SCID results from what deficiency?

-adenosine deaminase

67

What happens in SCID

-cells of the immune system are particularly affected by this deficiency
-condition results in patients being susceptible to infection by almost any microorganism, requiring living in a sterile bubble

68

What is the treatment for SCID?

Bone marrow transplant

69

What happens to the nitrogenous base in the salvage/degradation pathway?

The base can be shuttled back into purine synthesis or can be degraded to Uric acid

70

What enzyme does the excretion pathway of purine synthesis use?

Xanthine oxidase

71

Xanthine oxidase

-excretion
-intermediate is xanthine
-product is uric acid excreted in urine

72

Gout is the result of what?

-Hyperuricemia (elevated levels of uric blood
-accumulation of uric acid crystals in the joints
-leading to inflammation and gouty arthritis

73

What can cause Gout?

-underexcretion of uric acid (most common)
-which can be caused by: poor kidney function, acid-base balance imbalance, certain drugs
-overporduction of uric acid

74

Overproduction of uric acid treatment

Allopurinol

75

What does allopurinol do?

Treats gout in "overproducers" by inhibiting xanthine oxidase which produces uric acid

76

Hyperuricemia as a secondary condition

Can be secondary to many conditions such as high cell turnover in cancer patients being treated with various anti tumor drugs

77

Lesch-Nyah's syndrome

-deficiency in the purine salvage pathway
-defect in HGPRT
-deficit of purines
-extreme hyperuricemia

78

Symptom of Lesch-Nyhan

-severe mental retardation
-self destructive behavior
-self mutilation


Chewing off lips and fingertips
Scratching/gouging eyes
Severe gout symptoms

79

How can gout affect the eye?

Deposits tophi in
-the conjunctiva
-cornea
-iris
-sclera
-lens
-other eye tissue
-the formation of transparent vesicles
-bleeding in the subconjunctival space and vascular changes