Biochem: molecular Flashcards
What histones make up the nuclosome core?
H2A, H2B, H3, H4 (2 of each)
What amino acids are histones rich in?
lysine and ariginine, they give positive charge, bind negatively charged DNA
Which histone beads the nucleosomes in a string?
H1
What does histone methylation lead to?
inactivates transcription of DNA
What does histone acetylation lead to?
relaxes DNA coiling, allows for transcription
Which DNA bases are methylated? What purpose does this serve?
adenine and cytosine
allows mistmatch repair enzymes to distinguish between old and new strands in prokaryotes
What turns cytosine into uracil?
deamination
What amino acids are needed for purine synthesis?
glycine
aspartate (N)
glutamate (N)
(also need tetrahydrofolate and CO2)
What is needed to make the pyrimidines?
aspartate, carbamoyl phosphate-made of CO2, glutamine, ATP
What is the rate limiting step in pyrimidine synthesis?
CPSII
What enzyme does hydroxyurea inhibit?
ribonucleotide reductase
What enzyme does 6-MP inhibit?
glutamine PRPP amidotransferase
What enzyme does 5-FU inhibit?
thymidylate synthase (decreases dTMP)
What enzyme does MTX inhibit?
dehydrofolate reductase (decreases dTMP)
What does trimethoprim inhibit?
bacterial DHFR (decreases dTMP)
What causes orotic aciduria?
inability to convert orotic acid to UMP because of AR defect in UMP synthase
What are common findings in orotic aciduria patients?
increased orotic acid in urine, megaloblastic anemia that does not imporve with B12/folate, failture to thrive NO hyperammonemia (vs OTC deficiency)
How is orotic aciduria treated?
oral uridine administration
What is the result of adenosine deaminase deficiency?
excess ATP and dATP imbalances nucleotide pool which prevents DNA synthesis
this decreases lymphocyte count
What disease can adenosine deaminase deficiency cause?
SCID
AR
What happens when the enzyme HGPRT is deficient/absent?
defective purine salvage
results in excess uric acid production and de novo purine synthesis
What disease is caused by HGPRT deficiency? Sx? Inheritance?
Lesch Nyhan
XR
retardation, self mutilation, aggression, hyperuricemia, gout, choreoathetosis
What is Lesch Nyhan treated with?
allopurinol
What DNA repair machanism is mutated in xeroderma pigmentosa? what does this prevent?
nucleotide excision repair (endonucleases)
can’t repair pyrimidine dimers
increased risk of skin cancer