Nucleotide Biosynthesis and Salvage (Watts) Flashcards
what are some nucleotide functions? (3)
energy metabolism (ATP), enzyme cofactors (NAD+), signal transduction (cAMP)
what are some nucleic acid functions?
storage of genetic info (DNA), transmission of genetic info (mRNA), processing of genetic info (ribozymes), protein synthesis (tRNa/rRNA)
what is a nucleotide?
- nitrogeneous base
- sugar (pentose)
- phosphate group
nucleoside just base and sugar, no phosphate group
typically, where is the phosphate group attached? (carbon number)
what charge?
5’, negatively charged
in nucleotides, how it the pentose ring attached to the nucleobase?
beta N-glycosidic bond,
how can nucleotides be synthesize from amino acids, ribose-5-p, CO2, and NH3?
De novo.
what can nucleotides be salvaged from?
nucleobases
what do many parasites lack, causing them to rely on salvage nucleotide biosynthesis?
lack de nevo biosynthesis..
anti anti-parasite drugs inhibit salvage pathways
does the de novo pathway use free bases?
no,
with de novo pathway a purine base is built up atom by atom directly onto ribose structure..
while pyrimidines base is assembled first then attached to ribose
what are the two pathways of nucleotide biosynthesis?
de novo and salvage
with de novo purine synthesis, is the base made before attachment to ribose or during?
purine is made WHILE attached to ribose…
this is different from de novo synthesis of pyrimidines because those are made first then attached to ribose.
de novo biosynthesis of purines begin with what?
synthesis of PRPP= 5-phosphoribosyl-1-pyrophosphate with Glu
what is the first intermediate of de novo biosynthesis of purines ?
inosinate (IMP)
what two bases are synthesized from the intermediate inosinate?
adenine and guanine (purines)
what are the four allosteric regulators of de novo purine synthesis?
- IMP, AMP, and GMP which are products of glutamine-PRPP amidotransferase rxn
- excess GMP, which inhibits formation of xanthylate from inosinate by IMP dehydrogenase rxn
- GTP, limits conversion of IMP to AMP, and ATP limits conversion of IMP to GMP
- ADP and GDP, PRPP synthesis inhibited by these
Inosinate can form ___ or ___?
AMP or GMP
what is the intermediate of inosinate (IMP) to AMP?
adenylosuccinate,
IMP –> adenylosuccinate
via adenylosuccinate synthase and GTP
what is the intermediate of inosinate to GMP?
Xanthylate (XMP)
IMP–> XMP
via IMP dehydrogenase
then XMP–> GMP
via XMP-Glutamine amidotransferase + ATP, and GLn
Pyrimidines are made from what three things during de novo synthesis?
Asp, PRPP, and carbamoyl phosphate,
remember, with pyrimidines de novo synthesis, you make the pyrimidines FIRST, then attach to ribose-5-p
what is the first committed step of the pyrimidine de novo synthesis?
Asp + N-carbamoylphosphate,
via aspartate transcarbamoylase (ATCase)
some anticancer drugs target?
thymidylate synthase,
which catalyzes dUMP–>dTMP
what is the allosteric inhibitor of pyrimidine de novo synthesis?
ATCase is inhibited by its end-prods= CTP
accelerated by ATP
dUMP can be converted to dTMP via?
thymidylate synthase
if you have a deficiency in folic acid, what will be results?
causes decrease in thymidylate synthesis, (normally catalyzes UTP–>TMP)
so without folic acid, you have Uracil being incorporated into DNA, can cause cancer, heart disease, neurological impairment
