USMLE step 1 biochemistry

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Mahshid Mir, M.D. [2] Ribosomes are made of proteins and rRNA

• Eukaryotes → 60 and 40s = 80s
• Prokaryotes → 50 s and 30 s = 70 s
  • Have 23s in 50s

Translation

• Initiation
  • IF1, IF2, If3
    • Assist in assembly of smaller ribosomal subunit to first trna molecule
    • Methionine is always the start
    • f-Methionine in prokaryotes
    • IF-2 first binds to 30s and then to methionine tRNA. Then when 50s comes along, it hydrolyzes GTP on IF2 and allows 50s to attach to 30s
  • A site → Incoming aminoacyl TRNA binds
  • P site → Polypeptide binds (Growing chain)
    • First tRNA binds here
  • E site → Free tRNA (exit)
• Elongation
  • Incoming charged aminoacyl TRNA binds to A site
  • Elongation factor help incoming trna to bind to A site (Uses GTP)
  • 50s has peptidyl transferase transfers AA from p site to A site
    • In prokaryotes, activity is in 23s subunit of 50s rRNA
  • Translocation
    • Ribosome complex moves 3 nucleotides
    • tRNA + Peptide is moved from A site to P site
    • Newly uncharged tRNA from P side to E side
    • EF-G  → Eukaryotes
    • EF-2 in eukaryotes
      • Diptheria and exotoxin (Pseudomonas) inhibit this
• Termination
  • Stop codons
    • UGA, UAA and UAG
    • Signal to STOP
    • No new TRNA coming
    • Release factor binds to MRNA and hydrolyzes GTP and new polypeptide is released.
• Antibiotics
  • Aminoglycosides → Inhibit 30s subunit before initiation (No pairing with TRNA)
  • Linezolid → Inhibits initiation by binding to 50s subunit
  • Tetracycline
    • Bind to 30s subunit
    • Prevent aminoacyl TRNA from binding to A site
  • Chloramphenicol
    • Inhibits peptidyl transferase
    • Binds to 50s
  • Macrolides
    • Inhibits translocation by binding to 50s subunit
  • Clindamycin
    • Same as macrolides
  • Lincamycin
    • Bind to 50s and inhibit translocation
  • Streptrogranin
    • Bind to 50s and inhibit translocation
  • Buy AT 30 ,CCELL at 50
• Post translational modification
  • Trim terminals
  • Covalent modification
    • Glycosylation, hydroxylation, phosphorylation
    • Collagen → Hydroxylation of proline and lysine
  • Disulfide bonds
  • Protein folding
    • Primary structure → Chain
    • Secondary structure → Beta and alpha pleated
    • Tertiary structure