Nate's extra biochem flashcards
What does DNA methylation, Histone methylation and Histone acetylation do to transcription?
DNA methylation-represses transcription (Methylation of DNA Mutes DNA)
Histone methylation: can activate or repress transcription
Histone acetylation: Relaxes DNA coiling -> ACTIVATES transcription
What nucleotides are purines and which are pyrimidines? Which have 2 rings, which have 1?
Which nucleotide has a methyl group?
Which pair has 3 bonds? Which pair has 2 bonds?
Purines: PURe As Gold -> Adenine and Guanine. 2 rings
Pyrimidines: CUT the PY -> Cytosine, Uracil and Thymine 1 ring.
Thymine has a methyl group (THYmine meTHYl)
GC pairs have 3 hydrogen bonds. AT have 2 hydrogen bonds. > GC content means > melting point.
What gives DNA its neg charge? What gives histones their positive charge? Which histone is not in the nucleosome core?
DNA neg charge due to phosphate groups
Histones positive charge due to arginine and lysine
DNA and histones for ionic bonds
Histone H1 is a linker and is not in the nucleosome core.
Purine synthesis: what are the three sources of carbon? what are the two sources of nitrogen?
Carbon: tetrahydrofolate, glycine and CO2
Nitrogen: Glutamine, Aspartate
Pyrimidine synthesis needs?
Glutamine, Aspartate and CO2
How are purines synthesized? What drugs interfere with this pathway.
Ribose 5P —-PRPP synthetase–> PRPP —–PRPP amidotransferase (RL step**)—-> IMP —-Inosine monophosphate dehydrogenase—-> AMP and GMP.
6MP inhibits PRPP synthetase. Mycophenylate inhibits IMP dehydrogenase.
How are pyrimidines synthesized? What drugs interfere?
CO2 + Glutamine + ATP —CPS2** (RL step)—> Carbamoyl phosphate —> orotic acid. Orotic acid + PRPP —> UMP –> UDP —-Ribonucleotide reductase –> dUDP —> dUMP –Thymidylate synthase –> dTMP (this last reaction need THF).
THF is regenerated by DHF by DHFR. DHFR is inhibited by methotrexate and trimethoprim. Thymidylate synthase is inhibited by 5-FU. Ribonucleotide reductase is inhibited by hydroxyurea.
What are the cause of orotic aciduria? What are the clinical features? Tx?
Deficiency in UMP synthase causes inability to make UMP from orotic acid.
Orotic acid is increased in the urine. No hyperammonemia. Megaloblastic anemia (***DOES NOT IMPROVE WITH FOLATE OR B12). Failure to thrive.
Tx- bypass step -> give uridine (UMP).
Which enzyme converts guanine to GMP and hypoxanthine to IMP? Which enzyme converts adenine to AMP?
HGPRT converts guanine to GMP and hypoxanthine to IMP. APRT converts adenine to AMP. Both require PRPP.
Hypoxanthine Guanine PhosphoRibosylTransferase = HGPRT
Adenine PhosphoRibosylTransferase = APRT
What is the only molecule that can be made into hypoxanthine?
Inosine
How is adenosine made into inosine?
Adenosine deaminase (ADA)
What does a deficiency in adenosine deaminase cause?
ADA deficiency causes inability to break down adenosine causing increased ATP and dATP negative feedback on ribonucleotide reductase. DNA synthesis is inhibited and lymphocyte count decreases.
Autosomal recessive. Causes SCID (severe combine immunodeficiency) in KIDS -> low B and T cells.
Clinical features: Triad: Recurrent infections, Chronic diarrhea, Failure to thrive. Also, absence of thymic shadow.
What does a HGPRT deficiency cause?
Inability to convert guanine to GMP and hypoxanthine into IMP. Thus pushes guanine and hypoxanthine into formation xanthine —- xanthine oxidase —> uric acid.
This is Lesch-Nyhan syndrome. Autosomal recessive.
Clinical features- Hyperuricemia/ gout. CNS problems (retardation, self mutilation (lip biting is common), aggression and choreoathetosis.
Tx- Allopurinol (inhibits xanthine oxidase) helps with gout, but no tx for CNS problems.
What are silent DNA point mutations
mutation in the third position of the codon -> tRNA wobble so there is no change in the AA.
What are missense DNA point mutations?
mutation causes change in AA, but it is similar in structure to the AA it replaced.
