Biochem abnormal Amnio3
Terms
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Purine and Pyr
what bond links the base and sugar together in a Nt?
Sam donates what?
PAPS donates what -
bond - N-glycosidic link
Sam - methyl
PAPS - a sulfate donor -
PUR and PYR
IMP - whats the base
What does thioredoxin do? -
Base - H
Thioredoxin - co-enz reduces ribonucleotide reductase, an electron donor
is reduced by NADPH in thioredoxin reductase -
IMP-->AMP
requires? inhibited by?
IMP-->GMP
requires? inhibited by? -
imp-->AMP requires GTP inhibited by AMP
IMP-->GMP
first step (IMP->XMP) inhibited by GMP
second step (XMP->GMP) requires ATP - How do you get from amp to imp? gmp to imp?
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amp to imp - amp deaminase
gmp to imp - gmp reductase -
Ribonucleotide reductase
two regulatory sites
how is it regulated
What pharmacological drug acan inhibit ribonucleotide reductase? -
REgulator sites
1) activity site( + ATP, -dATP/dGTP)
2) specificity site - needs a spec allosteric positive affector (dTTP)
Hydroxyurea -
PUR and Pyr
ADA deficiency
what doeas ADA normally do?
Leads to higher levels of what molecule and subsequent inhibition of what?
CLinical manifestation? -
Adenosine deaminase deficiency - normally converts adenosine to inosine the catabolism of purines, inherited disorder, leads to higher dATP which then inhibits ribonucleotide reductase,
Clinical - SCIDS both t and b cells, 20% of these types of syndromes are from ADA deficiency -
PR/PY
draw the catabolism of the purines amp and gmp -
amp-->adenosine (nucleotidase)
adenosine -->inosine (ADA)
inosine--> hypoxanthine (PNP)
hypoxanthine --> Xanthine(XO)
GMP--> guanosine (nucleotidase)
guanosine-->Guanine (PNP)
guanine-->xanthine(guanase) - in what order are ring C and N's added in purine
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Glutamine [n]
glycine[c/n](ATP)
N10-H4-F[c]
Glutamine[n] (ATP mg2+
Ring closure (atp mg2+)
CO2[c]
Asp[n] (ATP)
N10-H4-F[c]
Ring Closure -
draw Pyrimidine synthesis
pg 106, remember CAD and UMP synthase
what is the committed step? -
good luck
commited - synthesis of carbamoyl aspartate by aspartate transcarbamoylase - What are the main reactios of the salvage pathway?
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Phosphoribosylate purine bases (APRT/HGPRT)pg 103
H or G --> IMP or GMP
Phorphorylate nucleosides(ie adenosine --> amp via adenosine kinase) - in what order are ring C and N's added in a pyrimidine?
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glutamine and CO2 (ATP)
Aspartic acid
ring closure
ALL HAPPEN IN CAD - adenosine --> inosine via what enz
- adenosine deaminase
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PU an PYR
how do you go from OMP to UMP?
from utp to ctp?
dUMP can arise from what two molecules? -
omp to ump - orotidylic acid decarboxylate
utp to ctp - aminate using CTP Sythetase
dUMP - dUDP and dCMP -
PRPP glutamyl amidotransferase
Purine/Pyrimidine anabolism/catabolism -
Purine Anabolism
adds glutamine to PRPP
COMMITTED/REGULATED
+PRPP
-end products -
PUR/PYR
what inhibits thymidylate synthase - Thymidylate synthase takes dUMP to TMP, 5-fluorouracil a Thymine analog inhibits thymidylate synthase,
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PUR.PYR
nucleic acids are degraded to Nt's by?
how are Nt's degraded to nucleosides?
how are Nucleosides degraded to R-1-P? -
degredation - via nucleases
Degradation - via nucleotidases
Degradation - via nucleoside phosphorylase - inosine --> hypoxanthine
- Purine Nucleoside Phosphorylase
- How does salvage inhibit de novo synthesis?
- decreases PRPP, and generates nucleoside monophosphates that inhibit PRPP glutamyl amidotransferase
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What does Carbamoyl phosphate synthetase II do?
CPSII -
first step in pyrimidine catabolism, co2/glutamine -->CAP
REGULATED - Guanosine-->Guanine
- Purine Nucleoside Phosphorylase
- what does aspartate transcarbamoylase do?
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second step in pyrimidine catabolism
CAP-->CAA
COMMITTED -
PY and P
describe the use of allopurinol - HX analog, competetive inhibitor of xanthine oxidase ( part of the pur catabolic pathway resulting in uric acid), increases hypo and xanthine levels , at the active site allopurinal is oxidized to oxypurinol, oxypurinol is not readily freed from the active site, sequestering XO, the oxypurinol that IS released is salvaged to a Nt that inhibits amidotransferase (PRPP glutamyl) thus inhibiting de novo sythesis so you cant make more to degrade
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PUR/PYR
Hereditary orotic aciduria
deficiency of what two reactions/ what enzyme
CLINICAL sypmtoms
treatment -
aciduria - inherited, pyr de novo synthesis, orotate decarboxylase and orotate phosphoribosyl transferase (UMP SYNTHASE) are deficient, increase OA excretion and [],
CLINICAL - failure to develop, anemia
TREATMENT - large amounts of uridine -
PUR/PYR
Lesch-Nyhan syndrome
deficiency of?
results in high [] of ?
Clinical signs? -
inherited x-linked,
Absent HGPRT activity
High [] of PRPP and therefore uric acid
Clinical syptoms - hyperuricemia w/gout, self-mutilation, aggressive, developmental delay, low motor skills, usuall die of renal failure - what does CTP synthetase do?
- converts utp--> CTP in pyrimidine anabolism, uses glutamine and atp
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PyR and PUR
PYR catabolism, how do you go from cytosine to uracil?
What can you detect in urine to measure DNA turnover? -
cyt- ura: deamination
beta-aminoisobutyrate, a unique degradation product of thymine -
describe the process of going from dUMP -->TMP
is it pur/pyr catabolism/anabolism? -
pyr anabolism
methylate the dUMP using THF
THF is oxidized to DHF
DHF is regenerated by DHF reductase (coENZ NADPH)
ser-->glu adds the 1C group to THF
Methotrexate inhibits DHF reductase -
PUR.PYR
Acyclovir - a modified guanosine, HIV and HSV herpes , inhibits replication, along with AZT