|
|
| Line 57: |
Line 57: |
| * Problem with urea cycle | | * Problem with urea cycle |
| Ribosomes are synthesized in the nucleus and transported into the cytoplasm. | | 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
| |
| 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
| |
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
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:
- 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.