Molecular Biology I

Question 1

What is the function of chromatin and how is it structured?

Answer 1

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)

Question 2

What amino acids make up histones?

Answer 2

Histones are POSITIVELY charged and composed mostly of Arginine and Lysine; DNA is negatively charged (p.64)

Question 3

When does DNA condense to form chromosomes?

Answer 3

During mitosis (p.64)

Question 4

What is the difference between heterochromatin and euchromatin?

Answer 4

Heterochromatin is condensed and transcriptionally inactive; Euchromatin is less condensed and transcriptionally active (p.64)

Question 5

What is the purpose of DNA methylationin prokaryotes and what part of DNA gets methylated?

Answer 5

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)

Question 6

What is the purpose of histone methylation?

Answer 6

Inactivates transcription of DNA (p.64)

Question 7

What is the purpose of histone acetylation?

Answer 7

Relaxes DNA coiling, allowing for transcription (p.64)

Question 8

What are some defining features of nucleotide structure?

Answer 8

Guanine has a ketone; Thymine has a methyl; deamination of cytosine makes uracil (p.64)

Question 9

What three amino acids and cofactors are necessary for purine synthesis?

Answer 9

Glycine, Aspartate, Glutamine + THF (p.64/5)

Question 10

How are purines constructed in de novo synthesis?

Answer 10

Start with a sugar + a phosphate (PRPP) and add a base (p.65)

Question 11

How are pyramidines constructed in de novo synthesis?

Answer 11

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)

Question 12

What is the function of Carbamoyl Phosphate?

Answer 12

Involved in de novo pyrimidine synthesis and the urea cycle (p.65)

Question 13

A deficiency in what enzyme will lead to an accumulation of carbamoyl phosphate which is then converted to orotic acid?

Answer 13

Ornithine Transcarbamoylase deficiency. Manifests with hyperammonemia. This is a key enzyme in the urea cycle (p.65)

Question 14

What amino acid is required for pyrimidine synthesis?

Answer 14

Aspartate (p.65)

Question 15

What enzyme does Hydroxyurea inhibit?

Answer 15

Ribonucleotide reductase (p.65)

Question 16

What is the mechanism of action of 6-Mercaptopurine (6-MP)?

Answer 16

Blocks de novo purine synthesis

Question 17

What is the mechanism of action of 5-Fluorouracil (5-FU)?

Answer 17

Inhibits thyimdylate synthase to decrease production of dTMP and halt DNA synthesis (p.65)

Question 18

What is the mechanism of action of Methotrexate (MTX)?

Answer 18

Inhibits dihydrofolate reductase to decrease production of dTMP (p.65)

Question 19

What is the mechanism of action of Trimethoprim (TMP)?

Answer 19

Inhibits bacterial dihydrofolate reductase to decrease dTMP (p.65)

Question 20

Describe the pathology of orotic aciduria.

Answer 20

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)

Question 21

Describe the symptoms of orotic aciduria.

Answer 21

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)

Question 22

What is the treatment for orotic aciduria?

Answer 22

Oral uridine administration (p.65)

Question 23

What clinical findings distinguish orotic aciduria from OTC deficiency?

Answer 23

Orotic aciduria –> increased orotic acid without hyperammonemia; OTC deficiency –> increased orotic acid with hyperammonemia (p.65)

Question 24

What purine salvage reactions require HGPRT + PRPP?

Answer 24

1.) hypoxanthine –> inosinic acid (IMP); 2.) Guanine –> Guanylic acid (GMP) (p.66)

Question 25

What purine salvage reaction requires APRT + PRPP?

Answer 25

Adenine –> Adenylic acid (AMP) (p.66)

Question 26

What purine salvage reactions requires Adenosine Deaminase (ADA)?

Answer 26

Adenosine –> inosine (p.66)

Question 27

What purine salvage reactions require Xanthine Oxidase?

Answer 27

1.) Hypoxanythine –> Xanthine; 2.) Xanthine –> uric acid (p.66)