Pyrimidine Nucleotide Synthesis Flashcards
What are the 3 pyrimidines
- Cytosine
- Thymine
- Uracil
How is the pyrimidine de novo pathway different from the purine de novo pathway (in terms of PRPP)?
Pyrimidine de novo pathway will assemble nitrogenous base FIRST then attach it to PPP
Describe the salvage pathway in pyrimidine de novo synthesis
Uracil is directly attached to a PRPP molecule by uracil phosphoribosyltransferase to make the UMP precursor
Describe step 1 in the de novo synthesis of pyrimidines
Carbamoyl phosphate is generated in the cytoplasm by CPS II
Describe step 2 in the de novo synthesis of pyrimidines
Aspartate trans-carbamoylase takes aspartate and carbamoyl phosphate and synthesizes carbamoylaspartate
Carbamoylaspartate contains all the atoms that will be incorporated into the 6 membered ring
Describe step 3 in the de novo synthesis of pyrimidines
2 steps take place in order to close the ring and form the first pyrimidine intermediate (orotate)
Describe step 4 in the de novo synthesis of pyrimidines
Once you have orotate it gets attached to the pentos sugar which comes from PRPP to form orotidylate
Describe step 5 n the de novo synthesis of pyrimidines
Orotidylate is converted to uridylate (UMP) which is the precursor for all other pyrimidine molecules
Describe step 6 in the de novo synthesis of pyrimidines
Once UMP is formed it can be converted to triphosphate (UTP)
Describe step 7 in the de novo synthesis of pyrimidines
UTP can be aminated to CTP
Why is CTP important in the regulation of the de novo synthesis pathway of pyrimidines
CTP will inhibit the first enzyme involved in this process aspartate trans-carbamoylase
How does CTP inhibit aspartate trans-carbamoylase?
- CTP increases the KM of aspartate trans-carbamoylase for aspartate
- If ATP concentrations = high inhibition by CTP is prevented*
How is RNA converted to DNA?
Ribonucleotide reductase
How does ribonucleotide reductase reduce ribonucleotides?
By getting electrons from NADPH