USMLE step 1 genetics

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

First

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 Dantrolene → Prevents release of calcium from SR of skeletal muscle Inhibit reuptake of norepinephrine: Cocaine TCA Ribosomes are synthesized in the nucleus and transported into the cytoplasm. 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