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26 Cards in this Set
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purine synth: regulation
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PRPP + Glu->(amidoxferase)->product
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Most important subs for purine synthesis
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glutamine
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Purine synth regulation
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end-product inhibition
purineMP->purineDP: A & G have their own enzyme purineDP->purineTP: common enzyme |
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Pyrimidine synthesis: difference btw it and purine synth
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base is built w/o being attached to sugar (purines are attached)
1 PP with 3 enzymatic sites does 1st three steps 1 PP w/ 2 enz sites last 2 steps |
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CPS I AND CPS II similarities
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sim: catalyze form. of carbamoyl (P) and both use ATP
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CPS I AND CPS II: location, pathway, N source, activator molecule
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CPS I:
mitochondria, urea cycle, ammonia, NAG CPS II: cytosol, pyrim. synth. amide of Glu, ATP, PRPP(+), UTP (-) |
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Urea cycle defects relationship to pyrimidines
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Urea prob->carbam(P) ->^CP->leaks to cytoplasm ->hyperammonia ->^pyrimidines ->kidney effects
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formation of CTP
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amination of UTP
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orotic aciduria: causes
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def in UMP synthase->accum and excr. of ^orotate
->regulation lost b/c ^ PRPP levels->make more orotate |
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orotic aciduria: Sx
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abnormal growth and development (heart and CNS probs)
megaloblastic anemia |
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orotic aciduria: treatment
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lots of uridine in diet->helps anemia and orotate excretion
restores Pyrim. level, production corrected (excretion not affected) |
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dNTP synth enzyme RR: coenzyme &
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thioredoxin = direct reducing agent
to recover reduced form: NADPH w/ thioredoxin reductase |
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dNTP synth: regulation
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RR: amnt of enzyme reg: ^ during S phase
2 types of allosteric sites |
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dNTP regulation: 2 types of allosteric sites
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overall enzyme activity: dATP is inhibitor
substrate specificity: one stim another-> balanced pool of dNTPs |
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dUMP to TMP: enzyme and cofactors
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dUMP + CH3-THF -> TMP + DHF
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pyrimidine: cancer therapy
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1. flouracil(uracial analog)->F-dUMP and v dTMP
=suicide inhibitor 2. Methotrexate (folate analog)->can't make THF from DHF->aff purines also |
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nucleic acid digestion: enzymes and 2 fates
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v pH->nucleases ->(P)diesterases -> nucleotidases ->nucleosidases
->salvaged(minor) or degraded (major) |
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salvage pathway: purines
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Hypoxanth and Guanine both use HGPRTase
Adenine: APRTase ___nine + PRPP->(PRTase)->_MP + PPi |
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Lesch-Nyham syndrome: causes and treatment
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v HGPRTase->^PRPP-> ^de novo purine synthesis
<2% activity: retardation <.2% activity: self-mutilation treat: allopurinol (removes uric acid) |
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Pyrimidine salvage:
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not as active as purine salvage
uracil+PRPP->(UPRTasess)->UMP+PPi Thymidine (n-side!)+ATP->(T-Kinase) ->TMP+ADP Cytosine not salvaged in humans |
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why thymidine salvage is different
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uses a nucleoside
direct (P) relatively specific for thymidine |
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cytosine salvage unique prop.
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not in humans
bact and fungi: Cytosine ->uracil flourocysteine=antimicrobial |
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purine degradation: enzymes
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PNP is same enzyme for all three
purine nucleoside phosphorylase all->uric acid->excreted or ->->urate->excreted |
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ADA deficiency
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SCID (bubble boy)
RR inhibited by dATP |
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GOUT
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^^uric acid (crystalizes @low temps)
prim cause: HGPRT def. sec. cause: renal diseases treatment: allopurinol so buildup is hypo and xanth (more soluble) |
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Purine nucleoside (P)lase deficiency
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v T-cell fxn
v uric acid w/ ^purines dGTP accumulates |