USMLE step 1 genetics

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Mahshid Mir, M.D. [2]

DNA synthesis

Histone → Contain lysine and arginine

DNA is negatively charged because of the negatively charged phosphate groups

Cytosine minus aminogroup = Uracil (Deamination)

G-C : 3 Hydrogen bonds. Higher melting points

A-T: 2 Bonds

Purine synthesis:

• You need glycine, glutamine and aspartate + tetrahydrofolate (Folic acid) + CO2
• Rate limiting step : Glutamine PRPP amidotransferase
• Carbon sources:
  • CO2, glycine, tetrahydrofolate
• Nitrogen sources
  • Aspartate + Glutamine

Pyrimidines:

Aspartate + carbamoyl phosphate (1 carbon and 1 nitrogen [glutamine]) + ATP

• Carbamoyl phosphate → Has 1 carbon and 1 nitrogen
• You need aspartate + CO2 + glutamine + ATP (Last 3 come from carbamoyl phosphate)
• Carbamoyl phosphate synthetase 2 (RATE LIMITING STEP)
• Start with orotic acid then add a base
• Carbon sources:
  • Aspartate
  • CO2
• Glutamine → Gives nitrogen

CPS 1 + CPS 2

• CPS 1
  • Mitochondria
  • Urea cycle
  • Use nitrogen from ammonia
• CPS 2
  • Cytosol
  • Pyrimidine synthesis
  • Use nitrogen from glutamine

Orotic aciduria

• Deficiency of UMP synthase
• AR
• Elevated oritic acid
• Megaloblastic anemia
  • Not corrected with B12 or folic acid
• No hyperammonemia
• Treat with uridine

Ornithine Transcarbomylase Deficiency

• Causes hyperammonemia
• Elevated orotic acid
• Problem with urea cycle

Ribosomes are synthesized in the nucleus and transported into the cytoplasm.