Final: nucleotide metabolism Flashcards
purines: where do carbons come from?
9 carbons from amino acids, 1 from CO2
purine synthesis overview
IMP is made then converted to purines
NADH from GMP synthesis
NADH is acquired energy → can contribute to ATP production in ETC
glutamine is a great…
amino donor
high ADP
low energy
cells won’t make new nucleotides
decrease ribose-5-phosphate pyrophosphokinase
high adenine or guanine (purines)
decreases activity of Gln-PRPP aminotransferase
high PRPP
activates Gln-PRPP aminotransferase
control at branch point
determines whether we get ATP or GTP
important because we need right ratio of nucleotides to decrease mutations
high AMP
blocks adenylosuccinate synthetase
high GMP
blocks IMP dehydrogenase
when is purine synthesis high?
when cells are about to divide
RBC don’t synthesize purines
PRPP synthesis regulation
inhibited by ADP and GDP
Gln-PRPP amidotransferase regulation
activated by PRPP
inhibited by AMP, ADP, and ATP at one regulatory site and GMP, GDP, and GTP at the other
purine synthesis is balanced
1) GMP and AMP slow their own production
2) GTP and ATP facilitate the synthesis of the opposite purine
purine synthesis step 2
PRPP to phosphoribosyl-beta-amine Enzyme: Gln: PRPP amido-transferase Glutamine + H2O to glutamate + PP PP (pyrophosphate is released and immediately degraded) Committed to purines!
pyrimidine: where do carbons come from
4/6 carbons from aspartate
which enzyme catalyzes committed step of pyrimidine synthesis?
CPS-II
CPS-II control
UDP and UTP feedback inhibit
PRPP and ATP allosterically activate
ribonucleotide reductase
deals with nucleotides
ultimate reducing power comes from NADPH
nucleotide catabolism and salvage
salvage of bases allows reuse of bases
when is ribonucleotide reductase turned on
high ATP
ATP binds to activity site to turn ON
what happens when dATP concentration rises?
dATP displaces ATP at activity site and turns enzyme OFF
regulation of dNTP synthesis occurs when
right before and during S phase of cell cycle
regulation of dNTP synthesis
1) increases general purine and pyrimidine synthesis by increasing levels of synthetic enzymes
2) express ribonucleotide reductase
3) express thymidylate synthase
4) express TMP kinase