Pyrimidine Synthesis and Salvage Pathways Flashcards
what are the 3 salvage pathways for nucleotides?
base to nucelotide
nucleoside to nucleotide
nuceloside to base to nucleotide
what enzyme turns adenine into AMP?
APRT
what enzyme turns hypoxanthine into IMP and guanine into GMP?
HGPRT
what do you need to help turn a base into a nucelotide?
PRPP
what enzyme turns a nucleoside into a free base?
purine nucleoside phosphorylase
if purine nuceloside phosphorylase is deficient…what builds up?
purine nucleosides, specifically toxic is build up of dGTP
What does buildup of dGTP come from and what does it cause?
purine nuceloside phosphorylase is deficienct so nucleoside building up
can lead to T cell issues
How does gout relate to PRPP synthetase?
if PRPP synthetase is mutated you can have over activity of it leading to extra PRPP and increased production of purines that can contribute to gout
how does glucose-6-phosphatase deficiency lead to gout? and what is the name of this disease?
it means you cannot send glucose into glycolysis and it forces more down pentose phosphate pathway leading to excess nucleotides and gout
von gierke disease
How does a problem with HGPRT lead to gout? What is this disease called? What is the diseases genetics?
you cannot salvage the guanine and hypoxanthine so these get broken down into uric acid instead
Lesch Nyhan
X linked recessive
allopurinol drug use and mechanism
treats gout by inhibiting uric acid synthesis by inhibiting Xanthine oxidase
febuxostate drug use and mechanism
also treats gout by inhibiting Xanthine oxidase and preventing uric acid synthesis
do purines or pyrimidines production start with a ribose backbone?
purines start with it and pyrimidines add it later
what is needed to make the pyrimidine ring?
aspartate, glutamine and CO2
what is the first step in pyrimidine synthesis?
glutamine, CO2 and phosphate turned into carbamoyl phosphate by CPS-II
what is the enzyme for the first step in pyrimidine synthesis?
CPS-II
what are the second and third steps in pyrimidine synthesis?
turn carbamoyl phosphate into carbamoyl aspartate and then turn carbamoyl aspartate into orotic acid
what is orotic acid?
the main precursor for pyrimidine molecules..it leads to UMP
What is hereditary orotic aciduria?
when you have issue with enzyme that changes orotic acid into nucleotides you get build up of orotic acid
What step is the committed step pyrimidine synthesis?
CPS II enzyme step…step 1
what can activate and what can inhibit CPS-II in pyrimidine synthesis?
PRPP activates
nucleotides inhibit
how do we make CTP from UTP?
using an enzyme called CTP synthetase
What are CTP and UTP degraded into? and what is this molecule useful for?
malonyl CoA
Malonyl CoA is involved in fatty acid synthesis
What is thymine degraded into? and what is this molecule used for?
methylmalonyl coa which can be made into succinyl CoA which can be used for krebs cycle
What is the salvage pathway for pyrimidines?
bases turned into nucleosides and then nucleosides into nucleotides
how do we turn nucleotides into deoxyribonucleotides?
using an enzyme call ribonucleotide reductase
what is unique about ribonucelotide reductase?
it only works to reduce ribonucleotides with two phosphates
what inhibits the ribonucleotide reductase?
hydroxyurea, which inhibits production of DNA…anti tumor
What are the two pathways to turn UDP into dUMP?
can either go directly with UDP to dUDP to dUMP
or can turn into CDP then dCDP then dCMP then dUMP
what molecule turns dCMP into dUMP?
dCMP deaminase
what is needed to turn dUMP into dTMP?
tetrahydrofolate
what molecule activates and what molecule inhibits ribonucleotide reductase?
ATP activated
dATP inhibits
Why does ribonucelotide reductase have two specific binding sites?
one for either activation or inhibition by ATP or dATP
one for determining what the preferred substrate is…as different nucleotides bind it prefers other nucleotides
mechanism of 5-fluorouracil?
anti tumor drug by inhibiting synthesis of thymidine
mechanism of methotrexate?
inhibits dihydrofolate reductase so cannot make thymidine
mechanism of 6-mercaptourine?
inhibits the glutamine phosphoribosyl amidotransferase that is committed step in purin synthesis so inhibits purines
mechanism of leflunomide?
inhibits production of orotate so inhibits production of pyrimidines
