Molecular Biology I Flashcards
What is the function of chromatin and how is it structured?
Condensed form of DNA to allow DNA to fit in the nucleus. Negatively charged DNA loops twice around positively charged histone octamers to form beads. The H1 unit ties the nucleosome beads together in a string and is not part of the nucleosome core (p.64)
What amino acids make up histones?
Histones are POSITIVELY charged and composed mostly of Arginine and Lysine; DNA is negatively charged (p.64)
When does DNA condense to form chromosomes?
During mitosis (p.64)
What is the difference between heterochromatin and euchromatin?
Heterochromatin is condensed and transcriptionally inactive; Euchromatin is less condensed and transcriptionally active (p.64)
What is the purpose of DNA methylationin prokaryotes and what part of DNA gets methylated?
Methylation allows for mismatch repair enzymes to distinguish between old and new strands in prokacyotes; Template strand cytosine and adenine are methylated in DNA replication (p.64)
What is the purpose of histone methylation?
Inactivates transcription of DNA (p.64)
What is the purpose of histone acetylation?
Relaxes DNA coiling, allowing for transcription (p.64)
What are some defining features of nucleotide structure?
Guanine has a ketone; Thymine has a methyl; deamination of cytosine makes uracil (p.64)
What three amino acids and cofactors are necessary for purine synthesis?
Glycine, Aspartate, Glutamine + THF (p.64/5)
How are purines constructed in de novo synthesis?
Start with a sugar + a phosphate (PRPP) and add a base (p.65)
How are pyramidines constructed in de novo synthesis?
Make a temporary base (orotic acid), add sugar + a phosphate (PRPP), modify base. Ribonucleotides are synthesized first and converted to deoxyribonucleotides by ribonucleotide reductase (p.65)
What is the function of Carbamoyl Phosphate?
Involved in de novo pyrimidine synthesis and the urea cycle (p.65)
A deficiency in what enzyme will lead to an accumulation of carbamoyl phosphate which is then converted to orotic acid?
Ornithine Transcarbamoylase deficiency. Manifests with hyperammonemia. This is a key enzyme in the urea cycle (p.65)
What amino acid is required for pyrimidine synthesis?
Aspartate (p.65)
What enzyme does Hydroxyurea inhibit?
Ribonucleotide reductase (p.65)
What is the mechanism of action of 6-Mercaptopurine (6-MP)?
Blocks de novo purine synthesis
What is the mechanism of action of 5-Fluorouracil (5-FU)?
Inhibits thyimdylate synthase to decrease production of dTMP and halt DNA synthesis (p.65)
What is the mechanism of action of Methotrexate (MTX)?
Inhibits dihydrofolate reductase to decrease production of dTMP (p.65)
What is the mechanism of action of Trimethoprim (TMP)?
Inhibits bacterial dihydrofolate reductase to decrease dTMP (p.65)
Describe the pathology of orotic aciduria.
A defect in UMP synthase that results in an inability to convert orotic acid to UMP via de novo pyramidine synthesis. An Autosomal Recessive condition (p.65)
Describe the symptoms of orotic aciduria.
Increased orotic acid in urine, megaloblastic anemia that does not improve with administration of B12 or folic acid, failure to thrive. No hyperammonemia (p.65)
What is the treatment for orotic aciduria?
Oral uridine administration (p.65)
What clinical findings distinguish orotic aciduria from OTC deficiency?
Orotic aciduria –> increased orotic acid without hyperammonemia; OTC deficiency –> increased orotic acid with hyperammonemia (p.65)
What purine salvage reactions require HGPRT + PRPP?
1.) hypoxanthine –> inosinic acid (IMP); 2.) Guanine –> Guanylic acid (GMP) (p.66)
What purine salvage reaction requires APRT + PRPP?
Adenine –> Adenylic acid (AMP) (p.66)
What purine salvage reactions requires Adenosine Deaminase (ADA)?
Adenosine –> inosine (p.66)
What purine salvage reactions require Xanthine Oxidase?
1.) Hypoxanythine –> Xanthine; 2.) Xanthine –> uric acid (p.66)
