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26 Cards in this Set

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purine synth: regulation
PRPP + Glu->(amidoxferase)->product
Most important subs for purine synthesis
glutamine
Purine synth regulation
end-product inhibition

purineMP->purineDP: A & G have their own enzyme

purineDP->purineTP: common enzyme
Pyrimidine synthesis: difference btw it and purine synth
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
CPS I AND CPS II similarities
sim: catalyze form. of carbamoyl (P) and both use ATP
CPS I AND CPS II: location, pathway, N source, activator molecule
CPS I:
mitochondria, urea cycle, ammonia, NAG

CPS II:
cytosol, pyrim. synth. amide of Glu, ATP, PRPP(+), UTP (-)
Urea cycle defects relationship to pyrimidines
Urea prob->carbam(P) ->^CP->leaks to cytoplasm ->hyperammonia ->^pyrimidines ->kidney effects
formation of CTP
amination of UTP
orotic aciduria: causes
def in UMP synthase->accum and excr. of ^orotate

->regulation lost b/c ^ PRPP levels->make more orotate
orotic aciduria: Sx
abnormal growth and development (heart and CNS probs)

megaloblastic anemia
orotic aciduria: treatment
lots of uridine in diet->helps anemia and orotate excretion

restores Pyrim. level, production corrected (excretion not affected)
dNTP synth enzyme RR: coenzyme &
thioredoxin = direct reducing agent

to recover reduced form: NADPH w/ thioredoxin reductase
dNTP synth: regulation
RR: amnt of enzyme reg: ^ during S phase

2 types of allosteric sites
dNTP regulation: 2 types of allosteric sites
overall enzyme activity: dATP is inhibitor

substrate specificity: one stim another-> balanced pool of dNTPs
dUMP to TMP: enzyme and cofactors
dUMP + CH3-THF -> TMP + DHF
pyrimidine: cancer therapy
1. flouracil(uracial analog)->F-dUMP and v dTMP
=suicide inhibitor

2. Methotrexate (folate analog)->can't make THF from DHF->aff purines also
nucleic acid digestion: enzymes and 2 fates
v pH->nucleases ->(P)diesterases -> nucleotidases ->nucleosidases

->salvaged(minor) or degraded (major)
salvage pathway: purines
Hypoxanth and Guanine both use HGPRTase

Adenine: APRTase

___nine + PRPP->(PRTase)->_MP + PPi
Lesch-Nyham syndrome: causes and treatment
v HGPRTase->^PRPP-> ^de novo purine synthesis

<2% activity: retardation
<.2% activity: self-mutilation
treat: allopurinol (removes uric acid)
Pyrimidine salvage:
not as active as purine salvage

uracil+PRPP->(UPRTasess)->UMP+PPi

Thymidine (n-side!)+ATP->(T-Kinase) ->TMP+ADP

Cytosine not salvaged in humans
why thymidine salvage is different
uses a nucleoside

direct (P)

relatively specific for thymidine
cytosine salvage unique prop.
not in humans

bact and fungi: Cytosine ->uracil
flourocysteine=antimicrobial
purine degradation: enzymes
PNP is same enzyme for all three

purine nucleoside phosphorylase

all->uric acid->excreted
or ->->urate->excreted
ADA deficiency
SCID (bubble boy)

RR inhibited by dATP
GOUT
^^uric acid (crystalizes @low temps)

prim cause: HGPRT def.
sec. cause: renal diseases

treatment: allopurinol so buildup is hypo and xanth (more soluble)
Purine nucleoside (P)lase deficiency
v T-cell fxn

v uric acid w/ ^purines

dGTP accumulates