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Biochem 1 > Nucleotide Metabolism > Flashcards

Nucleotide Metabolism Flashcards

(66 cards)

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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
How id PRPP made?
from ribose-5-phosphate, a product of the PPP | The pyrophosphate in PRPP is donated from ATP
26
What is the purpose of PRPP? | Which pathways can it be found?
- it is a high energy ribose-phosphate donor - de novo purine synthesis - de novo pyrimidine synthesis
27
How is ribose 5-phosphate produced via the oxidative pathway?
In the fed state, the oxidative pathway produces NADPH and ribose 5-phosphate (2:1 ratio) from G-6-P
28
How is ribose 5-phosphate produced via the non-oxidative pathway?
In the fasted state, the non-oxidative pathway produces ribose 5-phosphate only from glycolysis/GNG intermediates - it bypasses the oxidative reactions
29
Ribose-5-P and nucleotide synthesis is (independent/dependent) of dietary status?
independent
30
What are the AA that contribute to the purine ring?
glutamine glycine aspartate
31
What is the first step in the assembly of the purine ring structure?
- 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
What is the first committed step in the synthesis of purines?
transfer of an AA group from glutamine to PRPP forming phosphoribosyl amine
33
After the ring is formed in purine synthesis, were are additional atoms added
to the phosphoribosyl amine
34
After the ring is formed in purine synthesis, what is the second step?
Glycine is added, forming an amide bond with the nitrogen of phosphoribosyl amine. ATP hydrolysis provides energy to drive the reaction
35
Two of the carbon atoms in the purine ring are donated by ________
tetrahydrofolate (FH4)
36
The donor atoms carried by tetrahydrofolate comes from?
amino acids
37
What is the precursor of FH4?
folic acid
38
Generally, what happens when there is a folic acid deficiency?
inadequate DNA synthesis in proliferating cells
39
What happens when there is a folic acid deficiency in adults?
megaloblastic anemia - RBC precursors fail to divide properly
40
What happens when there is a folic acid deficiency in developing fetus?
neural tube defects
41
_______ deficiency mimics folate deficiency. Why?
vitamin b12 | w/o b12, our FH4 gets trapped in the form of methyl-FH4 = a form of functional FH4 deficiency
42
What are the two essential functions of B12?
Methyl acceptor | Methyl Donor
43
What is the function of B12 as methyl acceptor?
to recycle tetrahydrofolate - maintain adequate folate levels deficiency mimics folate deficiency megaloblastic anemia - easily detected
44
What is the function of B12 as methyl donor?
to provide methyl groups to SAM (S-adenosyl methionine) for a variety of methylation reactions deficiency causes neurological problems - often overlooked
45
What is the first purine ring structure produced by the de novo pathway?
Inosine monophosphate (IMP)
46
Which enzyme converts monophosphates to diphosphates and diphosphates to triphosphates using ATP as a phosphate donor?
nucleotide kinases
47
What is the enzyme specific for nucleoside diphosphates?
ribonucleotide reductase
48
Is ribonucleotide reductase base specific?
no
49
What type of inhibition is the purine de novo biosynthesis regulated by?
feedback inhibition
50
Which is the committed step in purine biosynthesis?
phosphoribosyl amine synthesis
51
What inhibits PRPP synthesis in purine biosynthesis?
ADP and GDP (acting at different allosteric sites)
52
What inhibits phosphoribosyl amine synthesis in purine biosynthesis?
AMP and GMP
53
Which nucleosides inhibit their own formation in purine biosynthesis?
AMP and GMP (from IMP)
54
Describe purine salvage
Nucleosides are converted to free bases by purine nucleoside phosphorylase Free bases can be converted back to nucleotides by phosphoribosyl transferases using PRPP
55
What is the dual role of purine salvage?
1. recycles purine ring - spares AA and reduces uric acid production 2. Main source of purine nucleotides for some cells
56
What is the key enzyme of purine salvage? | What does it do?
phosphoribosyl transferase | Converts free purine bases to nucleotides using PRPP as a ribose phosphate donor
57
What does APRT do?
adenosine phosphoribosyl transferase | -converts adenine to AMP
58
What does HGPRT do?
hypoxanthine-guanine phosphoribosyl transferase converts guanine to GMP and hypoxanthine to IMP
59
Can our bodies break down purine ring structure?
no
60
How do we get rid of purines?
In the liver, purines are converted into uric acid | Uric acid is transported by the blood to he kidney and excreted by urine
61
During the degradation of purines, what is GMP, AMP and IMP converted to?
GMP - guanine | AMP and IMP - hypoxanthine
62
What is guanine and hypoxanthine degraded?
converted to xanthine which is converted to uric acid
63
Why cant uric acid be broken down in humans?
we don't have uricase enzyme to break it down
64
What is a problem associated with uric acid?
- 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
Treatment of acute gout
NSAIDs
66
Treatment of chronic gout
allopurinol - suicide inhibitor of xanthine oxidase

Biochem 1 (22 decks)

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