Step1_BioChem Flashcards
[ssDNA Repair] Nucleotiide exision repair
specific endonucleases release the oligonucleotinde -containing damaged bases; DNA polymerase and ligase fill and reseal the gap (respectively)–> Repair BULKY helix distorign lesions
[ssDNA Repair] Nucleotiide exision repair - Clinical relevence
Mutated in Xeroderma Pigmentosum - which prevents repair of pyrimidine dimers because of UV light exposure
[ssDNA Repair] Base excision repair
Specific glycolases recognize and remove damaged bases, apurinic/apyrimidinic endonucleases cut DNA at both apurininc and apyrimidinic sites - empty sugar remoed – gap filled and resealed
[ssDNA Repair] Base excision repair - Clinical relevance
Repair of spontaneous/toxic deamination
[ssDNA Repair] Mismatch repair
Newly synthesized strand - recognized - mismatched nucleotides are removed - gap filled and resealed
[ssDNA Repair] Mismatch repair - Clinical relevance
Mutated in HNPCC
[dsDNA Repair] Nonhomologus end joining
Brings together 2 ends of DNA fragments to repair ds breaks. No requirment for homology
[dsDNA Repair] Nonhomologus end joining
Mutatedin ataxia telangiectasia
rRNA
most abundant
mRNA
longest
tRNA
smallest; CCA at the3’ end; anticodon end is opposite the aminoacyl end
aminoacyl-tRNA
synthase and binding of charged tRNA to codon –> responsible for accuracy of amino acid selection
Tetracyclines
bind 30S subunit –> prevent attachement of aminoacyl-tRNA
mRNA Start Codons
AUG (rarely GUG)
[mRNA start codon] Eukaryotes
Codes for methionine
[mRNA start codon] Prokaryotes
Code for formmymethionine (f-met)
mRNA Stop Codons
UGA, UAA, UAG
[Eukaryotes] RNA polymerase I
makes rRNA
[Eukaryotes] RNA polymerase II
makes mRNA; opens DNA at polymerase site; inhibted by alpha-amanitin (death mushroom)
[Eukaryotes] RNA polymerase III
makes tRNA
alpha-amanitin [Amanita phallodes - death cap mushroom]
inhibits RNA polymerase II –> severe HEPATOTOXICITY
tRNA Wobble
accurate base pairing only required in the first 2 nucleotide positions of an mRNA codon - may differ in the 3rd “wobble” posistion – code for the same tRNA/amino acid (2/2 degeneracy of genetic code)
[Protein Synthesis] Initiation
Activated by GTP hydrolysis; initiation factors help assemble 40S ribosomal subunit w/initiator tRNA –> released when mRNA and ribosomal subunit assemble with the complex
[Protein Synthesis] Elongation
(1) Aminoacyle -tRNA binds to A site (except for initiator methionine); (2) Ribosomal rRNA (“ribozyme”) - catalyze peptide bond formation –> transfer growing polypeptide to amino acid in A site; (3) Ribososome advances 3 nucleotide toward 3’ end of mRNA, moving peptidyl tRNA to P site (translocation)
[Protein Synthesis] Termination
Stop codon is recognized by release factor –> complete protein released frm the ribosome
[Abx - Protein synthesis inhibitors] Aminoglycosides
bind 30S and inhibit formation of initation complex and cause misreading of mRNA
[Abx - Protein synthesis inhibitors] Tetracyclines
bind 30S and block aminoacyl tRNA from entering the acceptor site
[Abx - Protein synthesis inhibitors] Chloramphenicol
binds 50S and inhibits petidyl transferase
[Abx - Protein synthesis inhibitors] Macrolides
binds 50S and prevent release of uncharged tRNA after it has donated its amino acid
[posttranslational modification] Trimming
Removal of N or C-terminal propeptides from zymogens to generate mature proteins
[posttranslational modification] Covalent alterations
P”, glycosylation, hydroxylation, methylation, and acetylation
[posttranslational modification] Proteasomal degradation
attachment or ubiquitin to defective prteins to tag them for breakdown
Drugs that act on Microtubules
Mebendazole/thiabendazole (antihelmenthic); Griseofulvin (antifungal); Vincristinevinblastine (anti-cancer); paclitazel (anti-brest cancer); cholchicine (anti-gout)
Chediak-Higashi Syndrome - pathophys
mutation in lysosomal trafficking regulator gene (LYST) - product required for micotuble-dependent sorting of endosomal proteins into late multivesicular endosome
Chediak-Higashi Syndrome - clinical
recurrent pyogenic infections, partial albinism, periferal neuropathy