Nucleotide metabolism Flashcards
nucleoside
linking a nitrogenous base to the 1’ position of the ribose ring
nucletodie
nucleoside added to phosphate at 5’ position of ribose ring
deoxyribonucleotide
hydroxyl group at 2’ position of ribose ring is replaced with H
de novo synthesis
makeing nucleotide from scratch
takes a lot of energy
salavage pathways
generation of nucleotides from free bases and nucleosides from diet
first step in purine synthesis
PRPP generation
committed step of purine synthesis
amidophosphoribosyltransferase forming PRA from PRPP
what is the first purine syntheiszed
IMP
what is IMP a precusor for
synthesis of both AMP and GMP
how are carbon and/or nitrogen atoms donating to de novo pathway
amino acids
what provides carbon and oxygen to de novo pathway
CO2
what serves as a donor of one-carbon groups to de novo pathway
N10-formyl THF
what is the rate limiting enzyme of GMP synthase
IMP dehydrogenase
what inhibits IMP dehydrogenase
GMP
what is the rate limiting enzyme of AMP synthesis
adenylosuccinate synthase
what inhibits adenylosuccinate synthase
AMP
how do AMP and GMP get converted into ATP and GTP
nucleoside 5’ monophosphate kinases and nucleoside 5’diphosphate kinases
what inhibits PRPPP synthetase
ADP and GDP
what is PRPP required for
synthesis of both purines and pyrimidines
what inhibits amidophosphoribosyltransferase
AMP and GMP
when is de novo purine synthesis limited
when purine nucleotides are abudent
incrase in PRPP do waht
stimulate de novo synthesis
what is the end product of purine metabolism
uric acid
how is uric acid excreted
kidney
hyperuricemia
excess uric acid in blood
what cause can reduced excretion of uric acid
renal insufficieny
metabolic acidosis
what can cause incrased production of uric acid
increased nucleotide turnover
diet rich in purine
how does EtOH affect uric acid
causes decreases excertion and increased production
is uric acid soluble or insoluble
insoluble
what is a possible consquence of increased uric acid
crystals of sodium urate deposite in joints, cause gouty arthritis
how do you treat hyperuricemia
allopurinol
how does allopurinol work
gets metabolized to oxypurinol which is a compoetitive inhibitor of xanthine oxidase
where does the synthesis of UMP take place
5 steps in cytoplasm, one in mitochondria
what is the first step in UMP synthesis
carbamoyl phosphate synthetase II
how do you get OMP to UMP
OMP decarbozylase
what are the first 3 steps of ump synthesis catalyzed by
CAD
what are teh last 2 steps of UMP synthase catalyzed by
UMP synthase
what causes orotic aciduria
defect in UMP synthase
symptoms of orotic aciduria
symptoms similiar to megaloblastic anemia
how do you treat orotic aciduria
pyrimidine supplementation
how do you get UTP to CTP
CTP synthase,
what does CTP use as a amino group donor
glutamine
how does UTP affect CTP synthase
as UTP levels increase, enzyme becomes more efficient at binding UTP
how does CTP affect CTP synthase
negative feedback
what catalyzes synthesis of deoxyribonucleutides
ribonucleotide reductase
what gets oxidized during ribonucleotide reductase
thioredoxin
wha tinhibits ribonucletodie reductase
hydroxyurea
what causes SCID
mutation in adenosine deaminase
do cells contain ribonucletodies of thymine
no
what catalyzes synthesis of dTMP
thymidylate syntahse
what happens when you inibt thymidylate synthase
prevent cell proliferation
inhibitor of thymidylate synthase
5-flurorourical
what happens when you degrate pyrimidine nucletodies
beta-amino acids
what is unique to thymine degration
beta-aminoisobutryate proudction
where does most de novo synthesis of nucleotides take palce
liver
what 2 enzymes do salavage of bases require
HGPRTase and APRTase
how do you get IMP in salaver pathway
hypoxanthine + PRPP
how do you get GMP in salvage pathway
Guanine + PRPP
how do you get AMP in salvage pathway
Adenine + PRPP
how does generation of IMP, GMP, and AMP by salvage pathways affect de novo synthesis
decreases it
what is lesch-nyhan syndrome caused by
deficeny of HGPRTase activity
symptoms of lesch-nyhan syndrome
hyperuricemia, uric acid stones, intellectual disablity, biting of fingers/lipis
what catalyzes pyrimidine bases and nucleosides
pyrimidine phosphoribosyltranserase
is cytosin salvaged in humans
no
what inhbiits CTP synthase
CTP
what inhbiits ribonucleotide reductase
NTPs and dNTPs
what inhbiits hypoxanthine guanine phosphoribosyltransferase
IMP and GMP
what inhibits adenine phosphoribosyltransferase
AMP