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Biochem 1 > Nucleotide Metabolism > Flashcards

Nucleotide Metabolism Flashcards

1
Q

What is the function of deoxyribonucleoside triphosphates?

A

synthesis of DNA

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2
Q

What is the function of ribonucleoside triphosphates?

A
  • synthesis of RNA

- energy metabolism

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3
Q

What are the deoxyribonucleoside triphosphates?

A

dATP, dGTP, dCTP, dTTP

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4
Q

What are the ribonucleoside triphosphates?

A

ATP, GTP, CTP, UTP

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5
Q

What is the purpose of ATP

A

Main energy currency of the cell

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6
Q

What is the purpose of GTP?

A

provides energy for protein synthesis

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7
Q

What is the purpose of UPT?

A

Provides energy for synthesis of glycogen and glycoproteins

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8
Q

What is the purpose of cTP?

A

Provides energy for phospholipid synthesis

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9
Q

Ribonucleotides are __________ of many enzymes

A

allosteric regulators

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10
Q

What are some ribonucleotide derivatives?

A
  • Cell regulators (cAMP, cGMP, poly ADP-ribose)

- Components of many coenzymes (NAD, FAD, coenzyme A)

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11
Q

Do non-proliferating cells require more ribonucleoside triphosphates or deoxyribonucleoside triphosphates?

A

Lots of ribonucleoside triphosphates
- RNA synthesis and metabolic roles

Very little deoxyribonucleoside triphosphates for DNA repair

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12
Q

Do proliferating cells require more ribonucleoside triphosphates or deoxyribonucleoside triphosphates?

A

Lots of deoxyribonucleoside triphosphates for synthesis of new DNA

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13
Q

What is the difference between nucleotides and nucleosides?

A

Nucleotides have a nitrogenous base, sugar and phosphate

Nucleosides have nitrogenous base and sugar

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14
Q

Nucleosides can pass in and out of cells but nucleotides cannot. Why?

A

Because it is phosphorylated

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15
Q

What are the purine ribo/deoxyribonucleosides?

A

(deoxy) adenosine = adenine + (deoxy)ribose

(deoxy) guanosine = guanine + (deoxy)ribose

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16
Q

What are the pyrimidine ribo/deoxyribonucleosides?

A

(deoxy)cytidine = cytosine + (deoxy)ribose

uridine = uracil + ribose

thymidine = thymine + deoxyribose

*D in pyrimidine, D in their names

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17
Q

What happens to dietary nucleotides taken up by intestinal cells? They are metabolized to ____

A

waste products eg uric acid

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18
Q

How do we get most of the purines and pyrimidines we need?

A

de novo synthesis - synthesized from scratch in our bodies

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19
Q

Where are purines and pyrimidines synthesized?

A

many tissues, especially the liver

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20
Q

After synthesis, how are purines and pyrimidines transported?

A

in the blood to other tissues in the form of nucleosides and free bases (has to be nucleosides b/c it isnt phosphorylated)

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21
Q

What happens to tissues that have low levels of de novo synthesis?
How do they get their purines/pyrimidines?

A

They import it from the liver = salvage pathways

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22
Q

What are some problems associated with deficiency of salvage pathwats?

A

immunodeficiency

neurological abnormalities

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23
Q

Where do the atoms that make up newly synthesized purine and pyrimidine come from?

A

amino acids

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24
Q

Describe de novo synthesis of purines

A
  1. Purine assembly
    - one atom at a time
    - takes place on a ribose phosphate scaffold, donated from PRPP
    - the completed ring structure first appears as a nucleotide, IMP
  2. IMP is converted to AMP and GMP
  3. Add more phosphates and convert ribonucleotides to deoxyribonucleotides
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25
Q

How id PRPP made?

A

from ribose-5-phosphate, a product of the PPP

The pyrophosphate in PRPP is donated from ATP

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26
Q

What is the purpose of PRPP?

Which pathways can it be found?

A
  • it is a high energy ribose-phosphate donor
  • de novo purine synthesis
  • de novo pyrimidine synthesis
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27
Q

How is ribose 5-phosphate produced via the oxidative pathway?

A

In the fed state, the oxidative pathway produces NADPH and ribose 5-phosphate (2:1 ratio) from G-6-P

28
Q

How is ribose 5-phosphate produced via the non-oxidative pathway?

A

In the fasted state, the non-oxidative pathway produces ribose 5-phosphate only from glycolysis/GNG intermediates
- it bypasses the oxidative reactions

29
Q

Ribose-5-P and nucleotide synthesis is (independent/dependent) of dietary status?

A

independent

30
Q

What are the AA that contribute to the purine ring?

A

glutamine
glycine
aspartate

31
Q

What is the first step in the assembly of the purine ring structure?

A
  • transfer of an AA group from glutamine to PRPP forming phosphoribosyl amine
  • Pyrophosphate is released in this step, so it has a large negative delta G
32
Q

What is the first committed step in the synthesis of purines?

A

transfer of an AA group from glutamine to PRPP forming phosphoribosyl amine

33
Q

After the ring is formed in purine synthesis, were are additional atoms added

A

to the phosphoribosyl amine

34
Q

After the ring is formed in purine synthesis, what is the second step?

A

Glycine is added, forming an amide bond with the nitrogen of phosphoribosyl amine. ATP hydrolysis provides energy to drive the reaction

35
Q

Two of the carbon atoms in the purine ring are donated by ________

A

tetrahydrofolate (FH4)

36
Q

The donor atoms carried by tetrahydrofolate comes from?

A

amino acids

37
Q

What is the precursor of FH4?

A

folic acid

38
Q

Generally, what happens when there is a folic acid deficiency?

A

inadequate DNA synthesis in proliferating cells

39
Q

What happens when there is a folic acid deficiency in adults?

A

megaloblastic anemia - RBC precursors fail to divide properly

40
Q

What happens when there is a folic acid deficiency in developing fetus?

A

neural tube defects

41
Q

_______ deficiency mimics folate deficiency. Why?

A

vitamin b12

w/o b12, our FH4 gets trapped in the form of methyl-FH4 = a form of functional FH4 deficiency

42
Q

What are the two essential functions of B12?

A

Methyl acceptor

Methyl Donor

43
Q

What is the function of B12 as methyl acceptor?

A

to recycle tetrahydrofolate - maintain adequate folate levels

deficiency mimics folate deficiency
megaloblastic anemia - easily detected

44
Q

What is the function of B12 as methyl donor?

A

to provide methyl groups to SAM (S-adenosyl methionine) for a variety of methylation reactions

deficiency causes neurological problems - often overlooked

45
Q

What is the first purine ring structure produced by the de novo pathway?

A

Inosine monophosphate (IMP)

46
Q

Which enzyme converts monophosphates to diphosphates and diphosphates to triphosphates using ATP as a phosphate donor?

A

nucleotide kinases

47
Q

What is the enzyme specific for nucleoside diphosphates?

A

ribonucleotide reductase

48
Q

Is ribonucleotide reductase base specific?

A

no

49
Q

What type of inhibition is the purine de novo biosynthesis regulated by?

A

feedback inhibition

50
Q

Which is the committed step in purine biosynthesis?

A

phosphoribosyl amine synthesis

51
Q

What inhibits PRPP synthesis in purine biosynthesis?

A

ADP and GDP (acting at different allosteric sites)

52
Q

What inhibits phosphoribosyl amine synthesis in purine biosynthesis?

A

AMP and GMP

53
Q

Which nucleosides inhibit their own formation in purine biosynthesis?

A

AMP and GMP (from IMP)

54
Q

Describe purine salvage

A

Nucleosides are converted to free bases by purine nucleoside phosphorylase

Free bases can be converted back to nucleotides by phosphoribosyl transferases using PRPP

55
Q

What is the dual role of purine salvage?

A
  1. recycles purine ring - spares AA and reduces uric acid production
  2. Main source of purine nucleotides for some cells
56
Q

What is the key enzyme of purine salvage?

What does it do?

A

phosphoribosyl transferase

Converts free purine bases to nucleotides using PRPP as a ribose phosphate donor

57
Q

What does APRT do?

A

adenosine phosphoribosyl transferase

-converts adenine to AMP

58
Q

What does HGPRT do?

A

hypoxanthine-guanine phosphoribosyl transferase
converts guanine to GMP
and hypoxanthine to IMP

59
Q

Can our bodies break down purine ring structure?

A

no

60
Q

How do we get rid of purines?

A

In the liver, purines are converted into uric acid

Uric acid is transported by the blood to he kidney and excreted by urine

61
Q

During the degradation of purines, what is GMP, AMP and IMP converted to?

A

GMP - guanine

AMP and IMP - hypoxanthine

62
Q

What is guanine and hypoxanthine degraded?

A

converted to xanthine which is converted to uric acid

63
Q

Why cant uric acid be broken down in humans?

A

we don’t have uricase enzyme to break it down

64
Q

What is a problem associated with uric acid?

A
  • uric acid is not very water soluble
  • decrease in rate of uric acid excretion from kidney/increase in rate of uric acid formation = accumulation of uric acid
  • monosodium urate crystals form in the synovial fluid of joints = gout
65
Q

Treatment of acute gout

A

NSAIDs

66
Q

Treatment of chronic gout

A

allopurinol - suicide inhibitor of xanthine oxidase

Biochem 1 (22 decks)

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