FA Biochemistry - Molecular (2)
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107 terms
Terms | Definitions |
|---|---|
 In the chromatin structure, which histones form the octamer, and which ties the nucleosome beads together in a string? | octamer = 2 sets of H2A, H2B, H3, H4; H1 ties nucleosome beads together |
| Octamer subunits consist primarily of which 2 amino acids? | lysine and arginine |
| Which type of chromatin is condensed, transcriptionally inactive, and sterically inaccessible? | HeteroChromatin = HighlyCondensed |
| Which type of chromatin is less condensed, transcriptionally active, & sterically accessible? | Euchromatin; Eu=tru; "truly transcribed" |
| What does PURe As Gold stand for? | Purine nucleobases = Adenine & Guanine |
| What does "CUT The PY" stand for? | PYrimidine nucleobases = Cytosine, Thymine, & Uracil |
| How many rings do purine hav? | 2 rings |
| How many rings do pyrimidines have? | 1 ring |
| How does cytosine become uracil? | Deamination of cytosine makes uracil |
| What polar group does guanine have? | A ketone |
| What non polar group does thymine have? | A methyl |
| Which bond is stronger, AT or CG? Why? What is the laboratory consequence of this? | CG (3 H-bonds) > AT (2 H-bonds); An ↑ in CG bonds will ↑ melting temperature |
| What 3 amino acids are necessary for purine synthesis? | Glycine, aspartate, & glutamine |
| What makes of a nucleoside? | Base + ribose = Nucleoside |
| What makes up a nucleotide? | base + ribose + phosphate = Nucleotide (linked by 3'-5' phosphodiester bond) |
| What are purines made from? | IMP precursor |
| What are pyrimidines made from? | Orotate precursor, with PRPP (phosphoribosyl pyrophosphate) added later |
| What is made first, ribonucleotides or deoxyribonucleotides? What enzyme is necessary to convert one to the next? | ribonucleotides are synthesized first and are converted to deoxyribonucleotides by ribonucleotide reductase |
| What 2 pathways is carbamoyl phosphate involved in? What enzyme deficiency leads to a build up of carbamoyl phosphate which is then converted to:__? | Carbamoyl phosphate is involved in: (1) de novo pyrimidine synthesis & (2) the urea cycle. Ornithine transcarbamoylase deficiency (urea cycle) leads to build up of carbamoyl phophate which is then converted to orotic acid. |
| Name 5 drugs that interfere with nucleotide synthesis: | (1) hydroxyurea: inhibits ribonucleotide reductase (2) 6-mercaptopurine: blocks de novo purine synthesis (3) 5-fluorouracil: inhibits thymidilate synthase (4) methotrexate: inhibits DHFR (5) Trimethroprin: inhibits bacterial DHFR |
| Inhibition of thymidilate synthase & inhibition of dihydrofolate reducatse (DHFR) leads to a decrease in what substance? | ↓dTMP |
| Which step in the de novo purine & pyrimidine synthesis pathway requires just aspartate? | orotic acid to UMP |
| Which step in the denovo purine & pyrimidine synthesis pathway requires aspartate, glycine, glutamine, & THF? | Ribose 5-P to PRPP |
| An inability to convert orotic acid to UMP would be caused by a deficiency of either of which two enzymes? What is this disease called and what is its inheritance? | orotic acid phosphoribosyltransferase or orotidine 5-phosphate decarbosylase; Dx = orotic aciduria (autosomal recessive) |
| What are the clinical findings in orotic aciduria? | ↑ orotic acid in urine; megaloblastic anemia (does not improve w/ administration of B12 or folic acid); failure to thrive; NO hyperammonemia (vs OTC deficiency) |
| What lab value can distinguish orotic aciduria from ornithine transcarbamoylase def? | OTC has hyperammonemia; orotic aciduria does not |
| What is the tx for orotic aciduria? | oral uridine administration |
| What does adenosine deaminase deficiency cause a build up of? What does this lead to? | excess ATP & dATP imbalances nucleotide pool via feedback inhib of ribonucleotide reductase; this prevents DNA synth & ↓ lymphocyte count (a major cause of SCID) |
| Adenosine deaminase def is an important cause of what immunodeficiency? | ↓DNA & ↓lymphocytes → SCID |
| Lesh-Nyhan is a defect in which enzyme? What are the biochemical results? | Defect in purine salvage d/t NO HGPRT; excess uric acid production |
| What is the enzyme HGPRT responsible for? | HGPRT converts: hypoxanthine → IMP & guanine → GMP |
| How is Lesh-Nyhan inherited? What are the clinical findings? | X-linked recessive; retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis |
| What reaction does adenosine deaminase normally catalyze? | Adenosine → Inosine |
| What does an unambiguous genetic code refer to? | each codon specifies only 1 amino acid |
| What does degenerate/redundant genetic code refer to? What is the exception to genetic redundancy? | more than 1 codon may code for the same amino acid; Methionine is the exception: it is encoded by only 1 codon (AUG) |
| What does commaless, nonoverlapping genetic code refer to? | read from a fixed starting point as a continuous sequence of bases |
| What does universal genetic code refer to and what are some exceptions? | genetic code is conserved throughout evolution, except for mitochondria, archaebacteria, mycoplasma, and some yeast |
| What is a silent mutation? | same AA, often base change in 3rd position of codon (tRNA wobble) |
| What is a missense mutation? | changed AA (convservative - new AA is similar in chemical structure) |
| What is a nonsense mutation? | change resulting in early stop codon |
| What is a frame shift? | change resulting in misreading of all nucleotides downstream, usually resulting in a truncated nonfxnal protein |
| What is the order of severity for the different types of mutations? | nonsense > missense > silent |
| Eukaryotic and prokaryotic DNA synthesis is _1_ and involves both _2_ and _3_ synthesis. | 1: semiconservative; 2: continuous; 3: discontinuous (Okazaki fragment) |
| For eukaryotes, where does replication begin? | begins at a consensus sequence of base pairs |
| What is the origin of replication? | A particular sequence of DNA where replication begins - may be single or multiple |
| Describe the replication fork | Y shaped region along the DNA template where leading and lagging strands are synthesized |
| What does helicase do? | unwinds DNA template at replication fork |
| What do the single stranded binding proteins do? | SS binding proteins prevent strands from reannealing |
| What do DNA topoisomerases do? | DNA topoisomerases create a nick in the helix to relieve supercoils created during replication |
| What does primase do? | Primase makes RNA primer on which DNA poly III can initiate replication |
| What does DNA polymerase III do? | prokaryotic only - elongates leading strand by adding deoxnucleoTIDEs to the 3' end. Elongates lagging strand until it reaches primer of preceding fragment. 3' → 5' exonuclease activity "proofreads" each added nucleoTIDE |
| DNA Polymerase III has 5'→3' (__1__) and proofreads with 3'→5' (__2__). | 1: synthesis; 2: exonuclease |
| What does DNA polymerase I do? | prokaryotic only - degrades RNA primer and fills in the gap with DNA |
| DNA Polymerase I (__1__) RNA primer with 5'→3' (__2__). | 1: excises; 2: exonuclease |
| What does DNA ligase do? | seals |
| How do fluoroquinolones work? (Abx) | inhibit DNA gyrase specific for prokaryotic topoisomerase |
| In which single strand DNA repair mechanism do specific endonucleases release the oligonucleotide containing damaged bases and DNA polymerase and ligase fill and reseal the gap? | Nucleotide Excision Repair |
| What disease occurs when there is a genetic defect in nucleotide excision repair? Describe the disease and its inheritance | Xeroderma Pigmentosum, prevents repair of thymidine dimers caused by UV light; Autosomal Recessive |
| In base excision repair, (__1__) recognizes and removes damaged bases and (__2__) cuts the DNA at (__3__) site to remove the empty sugar; then the gap is rilled an resealed. | 1: specific glycosylases; 2: AP endonuclease; 3: apyrimidinic site |
| Which SS DNA repair mechanism does this describe? - Unmehtylated, newly synthesized string is recognized, mismatched nucleotides are removed, and the gap is filled and resealed. | Mismatch repair |
| Mismatch repair is defective in which inherited disease? | Hereditary nonpolyposis colorectal cancer (HNPCC) |
| Is there any requirement for homology in nonhomologous end joining of ds DNA repair? | no: it's non homologous; brings together 2 ends of DNA fragments |
| In what direction are DNA and RNA both synthesized? | 5'→3' |
| Which carbon bears the triphosphate and the energy source for bond formation? | The 5' end of the incoming nucleotide |
| What is the target of the 3' hydroxyl attack? | The triphosphate bond |
| In which direction is protein synthesized? | N to C |
| What is the most abundant type of RNA? | rRNA |
| What is the longest type of RNA and what is the shortest type of RNA? | mRNA; tRNA |
| What does the start codon (AUG) code for in eukaryotes & prokaryotes? | euk: methionine; prok: formyl-methionine (f-Met) |
| What are the mRNA stop codons? | UGA, UAA, UAG |
| Which part of the DNA binds RNA polymerase and multiple other TFs upstream from gene locus? | Promotor- TATA box & CAAT box; AT rich sequence |
| What is the stretch of DNA that alters gene expression by binding of transcription factors? | Enhancer |
| This is the site of DNA where negative regulators bind: | Silencers |
| A promoter mutation commonly results in a dramatic (__) in the amount of gene transcribed. | A dramatic decrease in the amount of gene transcribed |
| In eukaryotes, what does RNA polymerase I make | rRNA |
| In eukaryotes, what does RNA polymerase II make? | mRNA |
| In eukaryotes, what does RNA polymerase III make? | tRNA |
| Which RNA polymerase opens DNA at promotor site? | RNA poly II |
| RNA polymerase can't proofread, but what can it do? | initiate chains; RNA polymerase II opens DNA at promoter site |
| In prokaryotes, what makes the different types of RNA? | 1 kind of RNA polymerase with multiple subunit complex makes all 3 kinds of RNA |
| Why does alpha amanitin cause liver failure and where is it found? | inhibits RNA polymerase II, found in death cap mushrooms |
| What 3 steps in RNA processing occur after transcription? | (1) capping on 5' end (7-methyguanosine) (2) polyadenylation on 3' end; ~200 A's (3) splicing out of introns |
| What is the initial transcript called and what is the capped and tailed transcript called? | Initial transcript: heterogeneous nuclear RNA (nhRNA); capped & tailed transcript: mRNA |
| Which enzyme involved in RNA synthesis does not require a template? What is the signal? | poly A polymerase; polyadenylation signal is AAUAA |
| What kind of RNA is transported out of the nucleus? | only processed RNA |
| Describe the 3 steps in pre-mRNA splicing of eukaryotes. | (1) Primary transcript combines w/ snRNPs & other proteins to form spliceosome. (2) Lariat shaped intermediate is generated. (3) lariate is released to remove intron precisely & join 2 exons |
| Patients w/ lupus make antibodies to ____. | Make antibodies to spliceosomal snRNPs |
| What part of the pre mRNA contains the actual genetic information coding for protein? | Exons |
| How many nucleotides is a tRNA & what form does the secondary structure take? | 75-90 nucleotides; Cloverleaf form |
| Which end of the tRNA is the amino acid bound to? | covalently bound to the 3' end (w/ CCA) |
| What does aminoacyl tRNA synthetase do to the AA before and after it binds to tRNA, and what happens if it's the wrong match? | Scrutinizes. Hydrolyzes the bond if it is the wrong match |
| What does a mischarged tRNA do? | reads usual codon but inserts wrong amino acid |
| How to tetracyclines work? | bind 30s subunit, preventing attachment of aminoacyl-tRNA |
| Accurate base pairing is required only in the first two nucleotide positions of an mRNA codon, so codons differing in the 3rd position may code for the same tRNA/AA due to degenerate genetic code. What is this called? | tRNA wobble |
| What initiates protein synthesis? | GTP hydrolysis, initiation factors (eIFs) help assemble 40S ribosomal subunit with initiator tRNA and are released with mRNA and the ribosomal subunit assemble with the complex |
| What happens in elongation of protein synthesis? | Aminoacyl-tRNA binds A site (except for initiator methionine); ribosomal rRNA catalyzes peptide bond formation, transfers growing peptide to AA in A site; ribosome advances 3 nucTIDE toward 3' end of RNA, moving peptidyl RNA to P site (translocation) |
| What happens in termination of proteins synthesis? | stop codon is recognized by release factor, and completed protein is released from ribosome |
| What ribosomes do eukaryotes have? | 40S + 60S → 80S (Eukaryotes, Even) |
| What ribosomes do prokaryotes have? | 30S + 50S → 70S (prOkaryotes, Odd) |
| What is the energy source for tRNA activation? | ATP (Activation) |
| What is the energy source for translocation? | GTP (gripping & going places) |
| How do aminoglycosides work? | by inhibiting formation of the initiation complex and cause misreading of mRNA |
| How does chloramphenicol work? | inhibits 50S peptidyltransferase? |
| How do macrolides and clindamycin work? | binds 50S, blocking translocation |
| What is trimming in posttranslational modifications? | removal of N or C termal propeptides from zymogens to generate mature proteins |
| What are covalent alterations in posttranslational modifications? | phosphorylation, glycosylation, hydroxylation |
| What is proteasomal degradation in posttranslational modification? | attachment of ubiquitin to defective proteins tag them for breakdown |
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