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Biochemistry 2 > Biosynthesis and Degradation of Nucleotides > Flashcards

Biosynthesis and Degradation of Nucleotides Flashcards

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1
Q

What is the first committed step in De Novo Synthesis of Purines?

A

Amination of PRPP

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2
Q

How many steps are there to purine nucleotides?

A

13

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3
Q

How is De Novo Synthesis of pyrimidines regulated?

A

by feedback inhibition
deoxyribose-5-phosphate to AMP

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4
Q

De Novo Synthesis is identical in all living organisms but there is one step different in?

A

eukaryotes

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5
Q

What does De Novo Synthesis of purines require?

A

amino acids
ribose-5-phosphate
CO2
NH4^+

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6
Q

Where do the carbon and nitrogen atoms come from to make the base of purine?

A

Aspartate
2 glutamines
glycine
CO2
2 formates

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7
Q

What are the key control steps in De Novo Synthesis of purines?

A
  1. Ribose 5-phosphate to PRPP
  2. Amination of PRPP
  3. IMP to AMP
  4. IMP to GMP
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8
Q

Which enzyme makes ribose-5-phosphate into PRPP?

A

ribose phosphate pyrophosphokinase

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9
Q

General process of making a 5 membered ring with de novo synthesis

A
  1. Animation (comitted)
  2. Amide bond to add glycine
  3. formylation
  4. amination
  5. cyclization/dehydration
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10
Q

Which enzyme is involved in the first committed step of animation in De Novo Synthesis?

A

Glutamine-PRPP Amidotransferase

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11
Q

What does Glutamine-PRPP Amidotransferase do?

A

hydrolysis of glutamine
amination of PRPP

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12
Q

Which enzyme is involved in the second step of the 5 ring De Novo synthesis?

A

GlycinAmide Ribonucleotide Synthetase

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13
Q

What does GlycinAmide Ribonucleotide Synthetase do?

A

uses ATP
attaches glycine to aminated PRPP

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14
Q

Which enzyme is involved in the third step of De Novo synthesis?

A

GAR transformylase

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15
Q

What does GAR transformylase do?

A

formylation of N-10-formylTHF to THF

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16
Q

Which enzyme is involved in the fourth step of De Novo Synthesis?

A

FGAR amidotransferase

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17
Q

What does FGAR amidotransferase do?

A

uses ATP
amination of FGAR into formylglycinamidine ribonucleotide (FGAM)

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18
Q

What is the fifth enzyme involved in De Novo Synthesis of purines?

A

FGAM cyclase/ AIR synthetase

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19
Q

What does FGAM cyclase (Air Synthetase) do?

A

uses ATP
cyclization and dehydration
5-amino-imidazole-ribonucleotide

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20
Q

What is the general process of building the 6 membered ring to form inosinate?

A
  1. Carboxylation
  2. Amide bond
  3. Cleave Fumarate
  4. Formylation
  5. Cyclization dehydration
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21
Q

Eukaryotes use AIR carboxylase which is a 1 step carboxylation. What do bacteria and fungi use?

A

CAIR synthetase and CAIR mutase which is a carboxylation over 2 steps

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22
Q

What does SAICAR synthetase do?

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A

amide bond formation

23
Q

What does SAIRCAR Lyase do?

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A

cleave fumarate

24
Q

What does AICAR Transformylase do?

25
What does IMP Synthase do?
cyclization
26
What does the conversion of AIR to CAIR require?
CO2
27
SAICAR synthetase
uses ATP amide bond formation second step of the 6 membered ring
28
SAICAR Lyase
cleaves fumarate third step of forming the 6 member ring
29
AICAR Transformylase
formylation of AICAR to FAICAR 4th step of the 6 membered ring formation
30
IMP Synthase
makes IMP cyclization and dehydration 5th step of the 6 membered ring formation
31
To go from IMP to to GMP what two reactions are involved?
oxidation followed by amination
32
To go from IMP to AMP what reaction is involved?
amination using aspartate
33
What does Pyrimidine synthesis start with?
Aspartate and PRPP
34
How many steps are involved in pyrimidine nucleotide synthesis?
7 steps
35
What is pyrimidine synthesis regulated by?
feedback inhibition
36
How is pyrimidine synthesis different from purine synthesis?
the ring is formed 1st then attached to PRPP
37
What are the seven general steps of pyrimidine synthesis?
1. Carbamoylation 2. Cyclization 3. Oxidation 4. Attach to PRPP 5. Decarboxylate 6. Phosphorylate twice 7. Amination
38
What does Aspartate transcarbamoylase do?
transfers carbamate and forms urea used in 1st step of pyrimidine synthesis
39
What does dihydroorotase do?
cyclization/ dehydration part of the second step in pyrimidine synthesis
40
What does dihydroorotase dehydrogenase do?
oxidation to the alkene using an NAD^+ third step in pyrimidine synthesis
41
What does orotate phosphoribosyltransferase do?
attaches a PRPP 4th step of pyrimidines
42
What does orotidylate decarboxylase do?
decarboxylate; removes CO2 5th step of pyrimidine synthesis
43
What do kinases in pyrimidine synthesis do?
add a phosphate group twice UMP->UDP->UTP 6th step in pyrimidine synthesis
44
What does cytidylate synthetase do?
Converts UTP->CTP with amination uses atp final step in pyrimidine synthesis
45
[CTP] decreases the activity of?
Aspartate transcarbamylase
46
A high [Asp] reduces what?
feedback inhibition of pyrimidine synthesis
47
Are there any committed steps in pyrimidine synthesis?
no
48
What does thymidylate synthase do?
catalyzes the methylation of dUMP to DTMP methyl group comes from N5N10-methylene-THF forms DHF that gets reduced to THF a drug target for cancer
49
What is dihydrofolate reductase?
a common drug target for cancer
50
What gets converted to FdUMP by the body?
fluorouracil
51
How does FdUMP inhibit thymidylate synthase?
it forms a covalent adduct
52
Methotrexate
100x greater affinity for DHFR competitive inhibitor
53
Trimethoprim
100,000x higher affinity for bacterial DHFR useful for bacterial infections

Biochemistry 2 (11 decks)

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