Pyrimidine Nucleotides and Anti-Folate Mechanisms Flashcards
how does the beginning of the pyrimidine pathway differ than that of purines?
the first 4 steps lead to the creation of orotate, which is a ring of C and N. the ribose phosphate group is only added after by the PRPP
what are the “building blocks” of a pyrimidine?
ATP, glutamine, CO2, aspartate, and PRPP
what is the important regulatory point in pryimidine synthesis?
carbamoyl synthetase 2- first step
inhibited by: UTP
activated by: ATP, PRPP
what is the final product of pyrimidine synthesis pathway?
UMP
how is CTP created?
UTP is converted using ATP and glutamine via the enzyme CTP synthase
how is a nucleotide monophosphate converted to a nucleotide triphosphate?
via sequential nucleotide kinases
describe pyrimidine salvage
pyrimidines from the diet and from cell turnover can be converted into nucleotides via pyrimidine phosphoribosyltransferase and PRPP
describe pyrimidine degradation
uracil is convereted into B-alanine, CO2, and NH3
thymine is converted to B-aminoisobutyrate, CO2, and NH3
these enter the citric acid cycle
ribonucleotide reductase
ribonucleotide diphosphates are converted into deoxyribonucleotide diphosphates
this is inhibited by dATP, activated by ATP
also regulated by separate binding sites for ATP, dATP, dTTP, and dGTP that cause reductions
this enzyme is important for maintaining the proper balance of dNTPs. too much is mutagenic but too little is lethal.
adenosine deaminase deficiency
adenosine to inosine is blocked, leading to cellular increases in adenosine and dATP.
dATP inhibits ribonucleotide reductase and cells cannot proliferate. results in SCID b/c of lack of b and t cells
how is dTMP created
ribonuclease reductase creates dUMP, but thats not used in DNA.
the enzyme thymidylate synthase converts dUMP to tUMP using 5,10- methylene-THF. in the process, THF is oxidized to dihyrdrofolate
