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30 Cards in this Set
- Front
- Back
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componants in nucleotides
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base- purine or pyrimidinne
nucleoside- base + sugar nucleotide- + phosphate (mono, di, or tri) eg. ATP, adenosine, adenine |
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functions of nucleotides (& sides & bases)
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make DNA/RNA
ATP signaling (cAMP) metabolism (NAD) NOT USED AS FUEL |
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DeNovo synthesis of purines
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R5P to base then add P's
PRPP is "holder" C-1 groups from THF N donors are glycine, aspartate, glutamine make PRPP then ring (5 ATP) IMP then AMP (via adenylosuccinate) & GMP (via XMP glutamine amidotransferase) kinases add P's (ATP) |
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regulation of purine synthesis
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AMP & GMP
feedback inhibition ADP (low energy) inhibs PRPP synthetase AMP, GMP, IMP (product) inhib amidiotransferase AMP inhibs IMP to AMP GMP inhibs IMP to GMP |
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enzymes for denovo synth of purines
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PRPP synthetase (inhib by ADP)
Glutamine-PRPP amidotransferase (inhib by AMP, IMP, GMP) |
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DeNovo synthesis of pyrimidines
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aspartate & carbamoyl P (urea cycle)
UMP to CDP & UDP make deoxy b4 making TMP |
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Thimidine monophosphate synthesis
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comes from CDP or UDP
must be deoxy first (ribonucleotide reductase) then add P (nside diphosphate kinase) dCTP to cUTP (deaminase) to dUMP (dUTPase) to dTMP (thymidylate synthase) |
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thymidylate synthase
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last step in converting CDP & UDP to dTMP (thru dCTP, dUTP, dUMP, dTMP)
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regulation of pyrmidine synthesis
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feedback inhibition
especially dATP for dTMP |
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ribonucleotide reductase
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pyrmidine synthesis (denovo)
gives deoxy form (only way to get dTMP) |
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storage of nucleotides
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very little
nucleotide synthesis is good med target |
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degredation of nucleotides
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use up leftovers
nucleotidase (tide to side) -gives MP hydrolyze off ribose or phosphorylyze off R1P |
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degredation of pyrmidines
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easily broken down to water soluble products
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degredation of purines
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xanthine oxidase
-Hypoxanthine to xan(hypoxanthine from AMP) -xanthine to uric acid (from Hypox or guanine) |
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Salvage pathway of nucleotides
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saves N
only for purines (gout) |
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enzymes for purine salvage
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Requires PRPP
APRT- -adenine & PRPP to AMP + PPi HGPRT -hypoxan (or guanine) + PRPP to IMP (or GMP) to PPi |
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diseases associated w/nucleotide metabolism
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ADA defic (SCID)
PNP defic (Ts prefd) Lesh Nyan (salvage) Gout (purine deg or synth) |
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bubble boy disease
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SCID
ADA deficiency AMP builds up 100 fold increase in dATP inhibits ribonucleotide reductase get deficient in ALL deoxy's No T's or B's |
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ribonucleotide reductase inhibited by
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high dATP
(found in ADA defic) |
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low ADA
low deoxy's T's & B's deficient |
ADA deficiency
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PNP deficiency
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less severe than ADA
only effects T's |
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clutzy child with neuro def's
self destructive |
Lesch-Nyan Syndrome
Classic deficient HGPRT (aka HPRT) |
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clutzy child with neuro def's
no self destructive |
Lesch-Nyan Syndrome
Varient |
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Lesch-Nyan Syndrome
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mutation in HGPRT (aka HPRT)
no IMP/GMP excess PRPP feed forward activation & less feedback inhibition leads to high levels AMP/GMP & Uric acid (die from kidney damage) |
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high PRPP
low IMP/GMP high AMP/GMP & uric acid |
lesch nyans
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causes of gout
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excess purine synth
-increased PRPP (overactive synthetase) -G6Ptase defic- increases PRPP via HMP (von Gierke) or impaired degredation -defic APRT or HGPRT or high levels purines - cell destriction (chemo) -kidney dysf -dehydration -diet (liver, dried beans) |
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MOA allopurinol
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inhibits xanthine oxidase
(decreases uric acid & H2O2) (pee out hypoxan & xan) |
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characteristics of gout
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high levels uric acid
increased H2O2 Tophi- deposits |
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tophi
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deposits of monosodium urate
big bump on toe |
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drugs using nucleotide metabolism pathway
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flurourasil-binds thymidylate synthase
methotrexate- inhibits DHF reductase (suicide) trimethoprim- binds BACTERIAL DHF reductase |
