USMLE step 1 genetics: Difference between revisions

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Latest revision as of 22:31, 26 September 2018

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.

@@ Line 1: / Line 1: @@
 __NOTOC__
 {{CMG}} {{MIR}}
-==First==
+==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:
+=== Purine synthesis: ===
-You need glycine, glutamine and aspartate + tetrahydrofolate (Folic acid) + CO2
+* You need glycine, glutamine and aspartate + tetrahydrofolate (Folic acid) + CO2
-Rate limiting step : Glutamine PRPP amidotransferase
+* Rate limiting step : Glutamine PRPP amidotransferase
-Carbon sources:
+* Carbon sources:
-CO2, glycine, tetrahydrofolate
+** CO2, glycine, tetrahydrofolate
-Nitrogen sources
+* Nitrogen sources
-Aspartate + Glutamine
+** Aspartate + Glutamine
-Pyrimidines: Aspartate + carbamoyl phosphate (1 carbon and 1 nitrogen [glutamine]) + ATP
-Carbamoyl phosphate → Has 1 carbon and 1 nitrogen
+=== Pyrimidines: ===
-You need aspartate + CO2 + glutamine + ATP (Last 3 come from carbamoyl phosphate)
+Aspartate + carbamoyl phosphate (1 carbon and 1 nitrogen [glutamine]) + '''ATP'''
-Carbamoyl phosphate synthetase 2 (RATE LIMITING STEP)
+* Carbamoyl phosphate → Has 1 carbon and 1 nitrogen
-Start with orotic acid then add a base
+* You need aspartate + CO2 + glutamine + ATP (Last 3 come from carbamoyl phosphate)
-Carbon sources:
+* Carbamoyl phosphate synthetase 2 (RATE LIMITING STEP)
-Aspartate
+* Start with orotic acid then add a base
-CO2
+* Carbon sources:
-Glutamine → Gives nitrogen
+** Aspartate
+** CO2
+* Glutamine → Gives nitrogen
 CPS 1 + CPS 2
-CPS 1
+* CPS 1
-Mitochondria
+** Mitochondria
-Urea cycle
+** Urea cycle
-Use nitrogen from ammonia
+** Use nitrogen from ammonia
-CPS 2
+* CPS 2
-Cytosol
+** Cytosol
-Pyrimidine synthesis
+** Pyrimidine synthesis
-Use nitrogen from glutamine
+** Use nitrogen from glutamine
-Orotic aciduria
-Deficiency of UMP synthase
+==== Orotic aciduria ====
-AR
+* Deficiency of UMP synthase
-Elevated oritic acid
+* AR
-Megaloblastic anemia
+* Elevated oritic acid
-Not corrected with B12 or folic acid
+* Megaloblastic anemia
-No hyperammonemia
+** Not corrected with B12 or folic acid
-Treat with uridine
+* No hyperammonemia
-Ornithine Transcarbomylase Deficiency
+* Treat with uridine
-Causes hyperammonemia
-Elevated orotic acid
+==== Ornithine Transcarbomylase Deficiency ====
-Problem with urea cycle
+* Causes hyperammonemia
-Dantrolene → Prevents release of calcium from SR of skeletal muscle
+* Elevated orotic acid
-Inhibit reuptake of norepinephrine:
+* Problem with urea cycle
-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)
-s 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