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28 Cards in this Set

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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?
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
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?
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?
glutamine and CO2 (ATP)
Aspartic acid
ring closure
ALL HAPPEN IN CAD
adenosine --> inosine via what enz
adenosine deaminase
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,
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
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?
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
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
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