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Flashcards in Pyrimidine Metabollism Deck (26)
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what molecules are pyrimidines

-thymine cytosine and uracil


difference between the association of the purine skeleton with PRPP and the pyrimidine skeleton and PRPP

-the purine skeleton is assembled ON the PRPP molecule
-whereas the pyrimidine skeleton is assembled prior to being attached to PRPP


what is a major regulatory step in the formation of pyrimidines? what are the products and the reactants

-formation of carbamoyl phosphate which happens in the cytoplasm and is ctalyzed by CPS2 from 2ATP, HCO3-, and glutamine


N carbamoyl aspartate is formed from what using what

-formed from carbamoyl phosphate and aspartate using aspartate transcarbamoylase


which reactions form the pyrimidine ring?

-dihydroorotase using N carbamoylaspartate, creating dihydroorotate
-dihydroorotate dehydrogenase using dihydroorotate to creat orotate


where does the ribose phosphate group come from? what molecule is it added to? and what enxyme does this? what happens next?

-comes from PRPP
-added to orotate
-catalyzed by orotate phosphoribosyl transferase
-orotidyl decarboxylase removes a carboxyl group from orotidylate (orotate + PRPP), creating uridylate (UMP)


adding phosphates to UMP

-forst uridylate kinase
-then the nonspecific nuclesoide diphosphate kinase


formation of CTP

-CTP synthase uses UTP, glutamine and ATP to produce CTP


where do the carbons come from on the pyrimidine ring

-3 carbons and an N come from aspartate
-1 C from bicarbonate
-1 N from glutamine


what are the first threee enzymes in the pyrimidine biosynthesis pathway
-what is special about them

-CPS2, aspartate transcarbamoylase
-they are all domains of the same polypeptide chain
-this is a multienzyme complex that facilitates the ordered synthesis of important compounds


how is pyrimidine salvage done?

-reversible conversion of bases to nucleosides catalyzed by a phosphorylase
-and then a nucleoside to a nucleotide via a kinase


why do we care less about pyrimidine catabolism?

-because in contrast to the uric acid produce in purine catabolism, pyrimidine catablsim doenst have any dangerous intermediates


during catabolism, nucleotides are first converted into what by what

-nucleosides by phosphotases


cytidine is converted to what by what during catabolism?

uridine by cytosine deaminase


uridine and thymidine are converted to what by what in catabolism

-free bases by pyrimidine nucleoside phosphorylase


how can you estimate the turnover of DNA in cancer patients which are undergoing a lot of DNA degradation during chemotherapy

-measure B-aminoisobuturate


what enzyme catalyzes the reaction producing deoxynucleosides?
-what does it need to do this and how is this cofactor formed?

-ribonucleotide reductase (RNR)
-thioredoxin, which is replenished by thioredoxin redcutase using NADPH


what is a inhibitor of tyrosyl radicals and what can this accomplish

-this is given to cancer patients hoping that the cell can not produce deoxys in order to replicate its DNA
-inhibits the RNR step


what regulates CPS2?

-inhibited by UTP
-activated by ATP, PRPP


what regulates OMP decarboxylase

-inhibited by UMP


orotic aciduria

-caused by the absence of either or both of the enzymes OPRT or orotidylate decarboxylase
-characterized by failure of normal growth and severe anemia due to inhibition of DNA replication due to lack of pyrimidines
-can treat by bipassing the block with either orotidylate (OMP) or UMP depending on the deficiency


control of the biosynthesis of dNTP's

-reduction of ribonucleotide diphosphates is controlled allosterically
-dATP inhibits RNR and ATP activates RNR
-this allows for fine tuning of the dNTP pool for DNA synthesis


adenosine deaminase deficiency

-causes death from infection before the age of 2
-patients lack both B and T lymphocyte function
-reason for immune dysfunction unknown
-associated with large build up of dATP (inhibitor of RNR), this may block activation of the immune systems since lymphocytes can not proliferate



-inhibits DHF reductase which catalyzes the reformation of THF which is used to make dTMP from dUMP
-anologue of folic acid, has a high affinity for DHF reductase
-valuable drug in the treatment of many rapidly growing tumors such as acute leukemia


consderation when treating someone with methotreate

-all rapidly dividing cells are vulnerable
-however they can be rescued by adding an alternative source of THF
-prolonged usage leads to resistance
-this means the dose should be sufficiently high in order to avoid the survival of mutant cells that become resistant



-this inhibits the enzyme thymiylate synthase which is directly responsible for the formation of dTMP using dUMP and methylene THF