Nucleotide Anabolism Flashcards
In addition to the salvage pathways, how else can purine and pyrimidines be synthesized? Where are the enzymes located in purine and pyrimidine synthesis?
de novo - from starting materials like CO2, NH3, and some of the AA Enzymes are in the cytosol
What are the sources of C and N atoms in pyrimidines?
Aspartate (donates 3C and 1N) Bicarb (donates 1C) Glutamine amide (donates 1N)
What are the steps in pyrimidine synthesis?
Amine from Glutamine Add CO2 Carbomyl Phosphate Add Aspartate Close the ring Orotic Acid Use PRPP to attach ribose-5-phosphate Remove CO2 to make Uridine (UMP) Cytosine or Thymidine From UMP, you can make Cytosine or Thymidine: UMP -> UDP -> UTP -> Cytosine UMP -> dUDP -> dUTP -> dUMP -> dTMP -> Thymidine
What vitamin do you need to make Thymidine, and why?
Folate, because it is the methyl source (N5, N10-methylene H4 folate is the source of CH3)
What does the drug 5-fluorouracil do to pyrimidine synthesis?
Prevents the cells from replicating. Used as a chemotherapy drug
How do pyrimidine and purine synthesis differ?
Pyrimidine: first we make the single ring, then add sugar, then add phosphate Purine: start with PRPP, add N, add and build up double rings from multiple sources
What are the sources of C and N atoms in purines?
Glutamine amide (2N) Glycine (1N, 2C) Aspartate amide (1N) Bicarb (1C) H4 Folate (2C)
What is the generic purine ring called?
IMP
How much ATP is required to synthesize a double ring purine?
4ATP (not including cost of PRPP)
What is the rate limiting step in pyrimdine synthesis?
CPS-2 is the rate-limiting step -glutamine + CO2 + 2ATP -> carbomyl phosphate + 2ADP + PPi
What happens if there is a defect in nucelotide anabolism?
Death (in utero)
What does GMP (Guanosine) require?
NAD, ATP, and NH2 from Gln
What does AMP (Adenosine) require?
GTP and NH2 from Asp
What comes from IMP?
GMP or AMP
What is the difference between Adenosine and Guanosine?
The placement of the amino group
How are the concentrations of AMP and GMP regulated?
The concentration of one affects synthesis of the other because you have to have A to make G and have to have G to make A. Keeps concentrations balanced
What does the antivrial drug Acyloguanosine (Acyclovir) do?
It impairs purine synthesis