DNA structure and purines Flashcards
chromatin vs chromosome ?
lots of chromatin together y3mel chromosome
what is a nucleosome and what appearance does it give ?
8 histone octomers with DNA wrapped twice around it to give it a bead on a string appearance
what allows for there to b a closed condensed link between nucleosomes ?
histone H1
what charge is there on DNA vs on histones and why ?
DNA is negatively charged due to phosphate groups
histones are positively charged due to lysine and arginine
in what phase of cell replication does the formation of DNA and histones happen ?
S phase
what is thee difference between heterochromatin and euchromatin?
heterochromatin is highly condensed and is transcriptionally inactive
euchromatin is less condensed and is transcriptionally more active
what is DNA methylation ?
adding a methyl group to cytosine
methylation mutes DNA
Makes it more condensed
less available for transcription
what type of chromatin is associated with methylation ?
heterochromatin
what clinical syndrome is associated with dysregulated DNA methylation ?
fragile X syndrome
what is thee difference between histone and DNA methylation ?
histone methylation is reversible
DNA methylation irreversible
what does histone methylation lead to the formation of ?
heterochromatin
what does histone acetylation do ?
it results in the formation off euchromatin as it removes the histones positive charge and relaxes the DNA coil allowing for more transcription to happen
an acetyl group is added to lysine
what does histone deacetylation do ?
does thee opposite off acetylation and deactivates DNA
what is the difference between nucleotides and nucleosides ?
nucleotides have a phosphate group nucleosides dont
what are the different types of nucleotides and mention the types of each ?
purines and pyrimidines
purines - adenine and guanine, hypoxanthine 2 rings
pyrimidines - thiamine, cytosine 1 ring
what controls the melting temperature of DNA ?
the number of CG bonds
what are the nitrogen and carbon sources for purine synthesis ?
nitrogen sources are glycine
aspartate
glutamine
the carbon sources
glycine
carbon dioxide
teetrahydrofolate
what diseases could benefit from histone deactylase inhibitors ?
huntingtons disease
some cancers show a high expression of histone deacetlyase
which base pairs are associated with methylation ?
repeating CG islands
a lack off methylation off CG islands results in triggering an immune response
what is the first step of purine de novo synthesis ?
ribose 5 phosphate
what are the steps in purine synthesis ?
start off with 5 ribose phosphate
then PRPP
then we get IMP, GMP, AMP
what is the clinical significance of histones ?
drug induced lupus - anti histone antibodies
in comparison to classic lupus where there is anti - dsDNA
in purine de novo synthesis where does the 5 ribose phosphate come from ?
from the HMP shunt
what are the intermediates in purine d novo synthesis ?
IMP
PRPP
what drugs intervene with purine synthesis ?
mycophenolate and ribavarin.
6MP
what does ribavarin do
and what ennzyme is inhibited by it ?
it is an antiviral that stops the conversion from IMP to GMP
inhibits IMP dehydrogenase
what is the mechanism of mycophenolate ?
immunosuppressants that stops the conversion of IMP to GMP
by inhibiting IMP dehydrogenase
what are the two fates of purines ?
either be converted into xanthine and excreted in uric acid
or salvages ( reused )
how does the salvage process happen ?
the purines are converted back to their monophosphate form in the presence of PRPP
in the purine salvage process how is guanine, adenine and hypoxanthine converted back to their monophosphate form ?
guanine and hypoxanthine see HGPRT in combination with PRPP to give MP and GMP
while adenine uses APRT and PRPP to give AMP
essentially what is PRPP ?
a nucleotide with no base
how does 6MP work ?
mimics the structure of guanine , so HGPT holds on to it and makes a mutant nucleotide
what syndrome is associated with a lack off HGPRT enzyme and what happens in this disease?
lesch nyhan syndrome
no purine salvage happens
also called juvenile gout
what is the classic presentation of lesch nyhan syndrome ?
young male
motor symptoms
self mutilation
gout
Hyperuricemia
Pissed off
Gout
Red orange crystals in urine
Tense muscles dystonia
what drug cannot be given with azathioprine ?
allopurinol both are xanthine oxidase inhibitors
what is the clinical association of adenosine deaminase deficiency ?
SCID
severe combined immunodeficiency disease
this happens due to
decrease ADA means mooore dATP
which will inhibit ribonucleotide reductasee (RNR)
decrease thee DNA preccursors which will inhibit thee productiion of lymphocytes
what is the form of inheritance inn lesch nyhan syndrome ?
x linked recessive
what is histone acetylation catalyzed by ?
HAT
