DNA Basics/Purines/Pyrimidines

Question 1

3 Negative and Positive Charges in DNA-histone interaction

Answer 1

DNA negatively charged because of PO4-

Histones positively charged because lysine and arginine

Question 2

Linker and Nucleosome Histones

Answer 2

H1 linker

H2A, H2B, H3, and H4 all nucleosome

Question 3

3 C Sources and 2 Other Substances Required for Purine Synthesis

Answer 3

3 C sources: Glycine, CO2, and THF

3 AAs are GAG - Glycine, Aspartate, Glutamine

Question 4

2/4 Substances for Pyrimidine Synthesis

Answer 4

Carbamoyl phosphate and aspartate (C source)

Carbamoyl phosphate comes from CO2 (C source) and glutamine

Question 5

Orotic Aciduria (what it is, what it causes, ddx, tx)

Answer 5

Defect in UMP synthase or something that converts orotic acid to UMP for pyrimidine synthesis. Get megaloblastic anemia and FTThrive that does NOT improve with B12 or Folate.
Will see orotic acid in urine also with ornithine transcarbamylase deficiency, but that will also have increased ammonia
Tx by bypassing and supplementing uridine in diet

Question 6

Hydroxyurea Mech

Answer 6

Inhibits ribonucleotide reductase which converts UDP to dUDP for Pyridiminde synth

Question 7

5-FU Mech

Answer 7

Inhibits Thymidylate synthase which converts dUMP to dTMP for pyrimidine synth

Question 8

2 DHF Reductase Inhibitors (and what that causes)

Answer 8

Methotrexate for euks and TMP for proks. Can’t regenerate THF for Thymidylate synthase for pyrimidine synth

Question 9

6-MP Mech

Answer 9

Inhibits PRPP Amidotransferase which converts PRPP to IMP for purine synth

Question 10

Mycophenolate/Ribavirin Mech

Answer 10

Inhibit IMP Dehydrogenase which makes converts IMP to GMP for purine synth

Question 11

Allopurinol Mech

Answer 11

Blocks xanthine oxidase which converts hypoxanthine to xanthine and xanthine to uric acid (to get out of purine salvage pathway). Used for gout

Question 12

Lesch-Nyhan Syndrome (what it is, symptoms, treatment)

Answer 12

Defective purine salvage due to XLR absent HGPRT which converts hypoxanthine to IMP and guanine to GMP. Get hyperuricemia/gout/aggression and self mutilation (LIP BITING)/intellectual diability/dystonia
Use allopurinol and shit

Question 13

Adenosine Deaminase Deficiency

Answer 13

Excesss ATP from lack of adenosine to insoine conversion in purine salvage pathway causes nucleotide imbalance from negative feedback so you prevent DNA synth and get SCID (immunodeficiency)

Question 14

Triad of SCID (& 1 other finding)

Answer 14

Severe recurrent infections
Chronic diarrhea
Failure to Thrive
Also absence of thymid shadow on CXR