Nucleotide Metabolism 2 Flashcards
What is the first step in pyrimidine synthesis?
Formation of carbamoyl phosphate (CAP)
Enzyme: carbamoyl phosphate synthetase II
What is the committed step in pyrimidine synthesis?
Formation of N-carbamoyl aspartate from aspartate and CAP
2nd Step
What are the rate limiting steps of pyrimidine synthesis?
1,2, and 3
Catalyzed by a trifunctional enzyme comples
What is the product of the first four steps of pyrimidine synthesis?
Orotic acid
What is the first pyrimidine nucleotide formed in synthesis?
Uracil monophosphate
What is the regulated step of pyrimidine synthesis?
First stem involving carbamoyl phosphate synthetase II
What are the regulators of CSII?
Inhibited by UTP
Stimulated by PRPP and ATP
What two molecules end up creating the pyrimidine ring?
Carbamoyl Phosphate and Aspartate
What is the cause of Orotic Aciduria?
Deficiency in orotate phosphoribosyl transferase or orotidylic acid decarboxylase
The two steps after the formation of orotic acid
What are the symptoms and treatment of orotic aciduria?
Apathy, repeated infections, urinary obstructions, magaloblastic anemia, abnormal erythrocytes
Excessive excretion of orotic acid, enlarged spleen and heart
Give uridine — can enter the pyrimidine salvage pathway
What is the function of thymidylate synthetase?
Converts deoxyUMP to deoxyTMP utilizing a THF derivative
What is the only reaction to generate dihydrofolate from tetrahydrofolate?
The reaction catalyzed by thymidylate synthetase
What is the function of 5-fluorouracil?
Suicide inhibitor of thymidylate synthetase
What is the clinical significance of tetrahydrofolate?
Target of many anti cancer drugs
Because dTTP is only used in DNA it is possible to target rapidly dividing cells over non-proliferating cells
What two enzymes are used in pyrimidine salvage?
Uridine-Cytidine Kinase
Thymidine Kinase
