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Biochemistry 2 > Biosynthesis and Degradation of Nucleotides > Flashcards

Biosynthesis and Degradation of Nucleotides Flashcards

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?

A

amide bond formation

23
Q

What does SAIRCAR Lyase do?

A

cleave fumarate

24
Q

What does AICAR Transformylase do?

A

formylation

25
Q

What does IMP Synthase do?

A

cyclization

26
Q

What does the conversion of AIR to CAIR require?

27
Q

SAICAR synthetase

A

uses ATP
amide bond formation
second step of the 6 membered ring

28
Q

SAICAR Lyase

A

cleaves fumarate
third step of forming the 6 member ring

29
Q

AICAR Transformylase

A

formylation of AICAR to FAICAR
4th step of the 6 membered ring formation

30
Q

IMP Synthase

A

makes IMP
cyclization and dehydration
5th step of the 6 membered ring formation

31
Q

To go from IMP to to GMP what two reactions are involved?

A

oxidation followed by amination

32
Q

To go from IMP to AMP what reaction is involved?

A

amination using aspartate

33
Q

What does Pyrimidine synthesis start with?

A

Aspartate and PRPP

34
Q

How many steps are involved in pyrimidine nucleotide synthesis?

35
Q

What is pyrimidine synthesis regulated by?

A

feedback inhibition

36
Q

How is pyrimidine synthesis different from purine synthesis?

A

the ring is formed 1st then attached to PRPP

37
Q

What are the seven general steps of pyrimidine synthesis?

A
  1. Carbamoylation
  2. Cyclization
  3. Oxidation
  4. Attach to PRPP
  5. Decarboxylate
  6. Phosphorylate twice
  7. Amination
38
Q

What does Aspartate transcarbamoylase do?

A

transfers carbamate and forms urea
used in 1st step of pyrimidine synthesis

39
Q

What does dihydroorotase do?

A

cyclization/ dehydration
part of the second step in pyrimidine synthesis

40
Q

What does dihydroorotase dehydrogenase do?

A

oxidation to the alkene using an NAD^+
third step in pyrimidine synthesis

41
Q

What does orotate phosphoribosyltransferase do?

A

attaches a PRPP
4th step of pyrimidines

42
Q

What does orotidylate decarboxylase do?

A

decarboxylate; removes CO2
5th step of pyrimidine synthesis

43
Q

What do kinases in pyrimidine synthesis do?

A

add a phosphate group twice
UMP->UDP->UTP
6th step in pyrimidine synthesis

44
Q

What does cytidylate synthetase do?

A

Converts UTP->CTP with amination
uses atp
final step in pyrimidine synthesis

45
Q

[CTP] decreases the activity of?

A

Aspartate transcarbamylase

46
Q

A high [Asp] reduces what?

A

feedback inhibition of pyrimidine synthesis

47
Q

Are there any committed steps in pyrimidine synthesis?

48
Q

What does thymidylate synthase do?

A

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
Q

What is dihydrofolate reductase?

A

a common drug target for cancer

50
Q

What gets converted to FdUMP by the body?

A

fluorouracil

51
Q

How does FdUMP inhibit thymidylate synthase?

A

it forms a covalent adduct

52
Q

Methotrexate

A

100x greater affinity for DHFR
competitive inhibitor

53
Q

Trimethoprim

A

100,000x higher affinity for bacterial DHFR
useful for bacterial infections

Biochemistry 2 (11 decks)

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