Nucleotide Synthesis Flashcards
rate limiting enzyme of purine synthesis
PRPP glutamyl amidotransferase
a rate limiting enzyme of pyrimidine synthesis
carbamoyl phosphate synthetase II
donors of atoms
in purine synthesis
- glutamine
- aspartate
- carbon dioxide
- glycine
- N10-formyltetrahydrofolate
donor of ribose-5 phosphate
to purine and pyrimidine synthesis
PRPP
sequence of steps
in purine synthesis
preformed ribose-5-phosphate comes then
–>
purine ring is constructed
parent molecule
purine
inosine monophosphate
products
purine synthesis
IMP –> GMP
•requires ATP
IMP –> AMP
•requires GTP
donors of atoms
in pyrimidine synthesis
glutamine
aspartate
carbon dioxide
sequence of steps
in pyrimidine synthesis
pyrimidine ring is constructed first, then attached to ribose-5-phosphate
parent molecule
pyrimidine
orotidine monophosphate
products
of pyrimidine synthesis
•UMP –> UTP –> CTP
•UMP –> dUMP
ribonucleotide reductase
•dUMP –> TMP
(thymidylate synthase)
converts ribose-5-phosphate
to its activated form
5-phosphoribosyl-1- pyrophosphate (PRPP)
PRPP synthetase
energy requirement of PRPP synthetase
ATP –> AMP
multisubunit enzyme that reduces nucleoside diphosphates into their deoxy forms
ribonucleotide reductase
ribonucleotide reductase requires
thioredoxin
NADPH
converts dUMP to thymine
thymidylate synthase
cofactor of thymidylate synthase
N5,N10-methylene tetrahydrofolate
thymidylate synthase is inhibited by
5-fluorouracil
drugs that inhibit nucleotide metabolism
- sulfonamides
- trimethoprim
- 5-fluorouracil
- methotrexate
- mycophenolate
inhibits xanthine oxidase
allopurinol
mycophenolate
used as
immunosuppresant to prevent graft rejection
structural analogs of PABA that competitively inhibit dihydropteroate synthase
sulfonamides
structural analog of folate, selectively inhibits bacterial dihydrofoate reductase
trimethoprim
metabolically converted 5-FdUMP which inhits thymidylate synthase
5-fluorouracil
injibits dihydrofolate reductase
which reduces tetrahydrofolate supply for synthesis of thymine
methotrexate
reversible inhibitor of IMP dehydrogenase , depriving T and B lymphocytes of nucleic acids
mycophenolate
building blocks of nucleic acids
nucleotides
