Lecture 7-Nucleotide Metabolism I (Nakai) Flashcards

1
Q

How does the cholera toxin work?

A
  • GTPase activity of a G protein usually will convert it from its active form (bound to GTP) to its inactive form (bound to GDP)
  • cholera toxin ADP-ribosylates the G-protein (using NAD+) disrupting its GTPase activity and the G-protein can’t turn off. Thus it constantly activates adenylyl cyclase
  • adenylyl cyclase forms cAMP and therefore PKA which stimulates release of digestive fluid and ions causing severe diarrhea and dehydration
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2
Q

What is required for de novo synthesis of nucleotides?

A
  • ribose phosphate moieties
  • aas
  • CO2
  • ammonia
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3
Q

The amount of ____ in a cell is indicative of how many purines need to be synthesized.

A

PRPP

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4
Q

Why is it that folate deficiency may lead to anemia and neural symptoms?

A
  • THF is required for 2 reactions in purine biosynthesis pathway so lack of folate impedes cells’ ability to replicate DNA
  • deficiency in RBCs since reticulocytes can’t divide
  • energy pools in NS may be insufficient for de novo synthesis of purins resulting in neural symptoms
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5
Q

What is the purpose of the Purine Nucleotide Cycle?

A
  • uses up AMP to shift equilibrium of the adenylate kinase reaction towards formation of ATP (from 2 ADP)
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6
Q

What are the 2 theories as to why AMP deaminase deficiency results in loss of energy?

A
  • you can’t use up the AMP from the adenylate kinase reaction to shift equilibrium towards production of ATP
  • Slowing down pathway between inosinic acid (IMP) –> adenylosuccinate –> adenylic acid (AMP) decreases use of this pathway and therefore you get less fumarate formed to refill CAC intermediates
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6
Q

What part of RNA contributes greatly to its plasticity that DNA doesn’t have?

A
  • 2’ OH
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7
Q

What regulates the PRPP synthetase

A

ADP

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8
Q

What regulates Glutamine-PRPP amidotransferase?

A
  • AMP
  • GMP
  • IMP
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9
Q

What feeds back specifically on the adenine pathway of purine synthesis to inhibit?

A
  • AMP
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10
Q

What feeds back specifically on the guanosine pathway to inhibit?

A
  • GMP
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11
Q

PRPP levels in cells is indicative of _____

A

how many purines need to be synthesized

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12
Q

What enzyme is involved in the committed first step of purine synthesis?

A

Glutamine PRPP amidotransferase

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13
Q

for the IMP –> AMP what aa is needed? What form of energy?

A
  • Asp

- GTP

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14
Q

for the IMP –> GMP what aa is needed? What form of energy?

A
  • Gln

- ATP

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15
Q

Which reaction of GMP synthesis is inhibited by GMP in this part of the pathway

A

IMP dehydrogenase

16
Q

What does the IMP –> AMP pathway make as a biproduct thats important and why?

A
  • fumarate

- a CAC intermediate

17
Q

What part of the AMP pathway is subject to feedback from AMP?

A
  • Adenylosuccinate synthetase
18
Q

AMP deaminase

A

deaminates AMP back to IMP–not the same thing as adenosine deaminase

19
Q

myadenylate deaminase deficiency

A
  • people run out of E quickly and can’t sustain vigorous exercise
  • lacking adenosine deaminase so you’re not feeding AMP into the purine nucleotide cycle
20
Q

What does adenylate kinase do?

A
  • converts 2 ADP –> ATP + AMP and the AMP goes into the purine nucleotide cycle (which drives this reaction forward)
21
Q

What is the Purine nucleotide cycle?

A
  • IMP –>(adenylosuccinate synthetase) –> Adenylosuccinate –> (adenylosuccinate lyase) –> AMP –> (AMP deaminase) –> IMP
22
Q

Other than using up AMP from the adenylate kinase reaction what is another theory about how the Purine nucleotide cycle generates energy?

A
  • it produces fumarate in the adenylosuccinate lyase reaction
23
Q

Whats the regulatory step in pyrimidine biosynthesis? What aa does it require?

A
  • CPS II reaction

- Gln

24
Q

What activates CPS II?

A
  • ATP

- PRPP

25
Q

What inhibits CPS II?

A
  • UDP

- UTP

26
Q

In pyrimidine synthesis, UMP has feedback on ______. What reaction does this enzyme orchestrate?

A
  • oratidylate decarboxylase

- oratidylate –> UMP