Lecture 7-Nucleotide Metabolism I (Nakai) Flashcards
How does the cholera toxin work?
- 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
What is required for de novo synthesis of nucleotides?
- ribose phosphate moieties
- aas
- CO2
- ammonia
The amount of ____ in a cell is indicative of how many purines need to be synthesized.
PRPP
Why is it that folate deficiency may lead to anemia and neural symptoms?
- 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
What is the purpose of the Purine Nucleotide Cycle?
- uses up AMP to shift equilibrium of the adenylate kinase reaction towards formation of ATP (from 2 ADP)
What are the 2 theories as to why AMP deaminase deficiency results in loss of energy?
- 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
What part of RNA contributes greatly to its plasticity that DNA doesn’t have?
- 2’ OH
What regulates the PRPP synthetase
ADP
What regulates Glutamine-PRPP amidotransferase?
- AMP
- GMP
- IMP
What feeds back specifically on the adenine pathway of purine synthesis to inhibit?
- AMP
What feeds back specifically on the guanosine pathway to inhibit?
- GMP
PRPP levels in cells is indicative of _____
how many purines need to be synthesized
What enzyme is involved in the committed first step of purine synthesis?
Glutamine PRPP amidotransferase
for the IMP –> AMP what aa is needed? What form of energy?
- Asp
- GTP
for the IMP –> GMP what aa is needed? What form of energy?
- Gln
- ATP
Which reaction of GMP synthesis is inhibited by GMP in this part of the pathway
IMP dehydrogenase
What does the IMP –> AMP pathway make as a biproduct thats important and why?
- fumarate
- a CAC intermediate
What part of the AMP pathway is subject to feedback from AMP?
- Adenylosuccinate synthetase
AMP deaminase
deaminates AMP back to IMP–not the same thing as adenosine deaminase
myadenylate deaminase deficiency
- 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
What does adenylate kinase do?
- converts 2 ADP –> ATP + AMP and the AMP goes into the purine nucleotide cycle (which drives this reaction forward)
What is the Purine nucleotide cycle?
- IMP –>(adenylosuccinate synthetase) –> Adenylosuccinate –> (adenylosuccinate lyase) –> AMP –> (AMP deaminase) –> IMP
Other than using up AMP from the adenylate kinase reaction what is another theory about how the Purine nucleotide cycle generates energy?
- it produces fumarate in the adenylosuccinate lyase reaction
Whats the regulatory step in pyrimidine biosynthesis? What aa does it require?
- CPS II reaction
- Gln
What activates CPS II?
- ATP
- PRPP
What inhibits CPS II?
- UDP
- UTP
In pyrimidine synthesis, UMP has feedback on ______. What reaction does this enzyme orchestrate?
- oratidylate decarboxylase
- oratidylate –> UMP
