First Aid: Molecular Biochem Flashcards Preview

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Flashcards in First Aid: Molecular Biochem Deck (29):
1

Stop codons

UAG, UAA, UGA

mutation to any of these is a "nonsense" mutation

2

Telomere code

TTAAGGG

3

start codons + what they code for

usually AUG

rarely GUG

codes for Met in euk

for N-formyl Met in prok

4

Nucleotide excision repair

enzymes

when it happens

disease(s)

  • endonucleases release the damaged bases; DNA polymerase and ligase repair
  • happens in G1
  • xeroderma pigmentosum

5

RNA polymerase types + inhibitors (4)

  1. RNAP 1 - makes rRNA; in nucleolus
  2. RNAP 2 - makes mRNA; alpha-amantin inhibits
  3. RNAP 3 - makes tRNA + 5s rRNA
  4. Prokaryotic RNAP - makes all kinds of RNA

rifampin inhibits DNA-dep RNAP in prokaryotes; actinomycin D inhibits RNAP in prok/euk

6

what 3 processes are done to hnRNA (heterogenous nuclear) in the nucleus before it becomes mRNA?

  1. 7-methylguanosine capping - 5' end
  2. polyadenylation - 3' end; ~200 As
  3. intron splicing

7

Base Excision Repair enzymes

what kind of damage do they repair + when?

what are they?

Repair spontaneous / toxic deamination throughout whole cell cycle

  • Glycosylase - removes altered base -> apurinic/-pyrimidinic site made
  • AP-Endonuclease - cleave 5' to remove 1+ NTs
  • Lyase - cleaves 3'
  • DNA-Polymerase-beta - fills gap
  • Ligase - seals
  • (mnemonic = GEL PLease)

8

Mismatch Repair Enzymes

how they work + when?

defective in what disease?

  • in S phase > recognize new strand, remove mismatched NTs, fill + seal gap
  • defective in Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer, HNPCC)

9

Double stranded DNA repair types (2)

how they work + diseases in which they are defective

  1. NHEJ - brings together 2 ends of DNA fragments; no homology req; may lose DNA
    • def. in ataxia telangectasia + Fanconi anemia
  2. Homologous Recomb. - 2 homolog DNA duplexes > damaged dsDNA strand repaired using complementary strand from homolog; no loss of NTs
    • defective in BRCA1 mut. (breast/ovary cc.)

10

Missense mutation

what is it + ex of disease

  • mutation that changes an AA
  • "conservative" if new AA is similar structure
  • sickle cell anemia is Glu > Val missense

11

Diff btwn promoters + enhancers + silencers

  • Promoter - RNA pol II and TFs bind upstream from gene (AT-rich, TATA or CAAT box)
  • Enhancer/Silencer - activator/repressor proteins bind sites close to/far from/within intron of gene

12

RNA processing

3 processes (where?) 

initial hnRNA (heterogenous nuclear) is modified in nucleus to become mRNA

  1. 5' cap - with methyl-guanosine
  2. polyadenylation - 3' tail of ~200 As
  3. intron splicing

13

mRNA quality control

where + how?

at cytoplasmic processing bodies (P-bodies)

  • exonucleases, decapping enzymes and miRNAs
  • mRNA may then be degraded or stored in p-body for later translation

14

explain process of pre-mRNA splicing

3 steps

  1. Spliceosome formation - primary transcript combines with snRPs and other proteins
  2. 5' cleavage - 5' end of intron cleaved; forms looped intermediate
  3. 3' cleavage - releases intron loop + exon ends join

15

examples of diseases of abnormal alternative splicing

(4)

  1. beta thalassemia
  2. Gaucher disease
  3. Tay-Sachs disease
  4. Marfan  syndrome

as well as some cancers

16

miRNAs

what are they, what do they do, how do they affect disease

  • small, conserved, noncoding RNA
  • posttranscriptionally reg gene expression by targeting 3' UTR on some mRNAs for degradation and translation repression
  • abnormal expr. of miRNAs targeting tumor suppressor gene products > cancer

17

tRNA structure

  • 75-90 NTs, cloverleaf shape
  • anticodon on one end binds mRNA codon, 
  • 3' aminoacyl end opposite... with CCA acceptor stem + many chemically modified bases
  • T-arm - binds tRNA to ribosome with TPsiC (ribothymidine, pseudouridine, cytidine)
  • D-arm - has dihydrouridine residues needed for tRNA recognition by aminoacyl-tRNA synthetase

18

enzyme which binds AA to tRNA

what does it do + how?

aminoacyl-tRNA synthetase

  • "charges" tRNA with proper AA; there is 1 AA-tRNA synthetase per AA + it uses ATP to charge
  • "scrutinizes" AA before + after tRNA binding + hydrolyzes bond if it is wrong
  • formed AA-tRNA bond has the E necessary for later peptide bond formation

19

Protein synthesis

3 steps, what's the first one + its details?

Initiation, Elongation + Termination

  • euk. initiation factors (eIFs) identify 5' cap or internal ribosome entry site (IRES) located anywhere on mRNA, often 5' UTR
  • eIFs help assemble 40s with initiator tRNA + release when 60s assembles w/ complex
  • requires GTP!

(remember ATP for Activation / charging of tRNA and GTP for Gripping/Going places ... translocation)

20

how do euk and prok ribosomes differ?

what direction are proteins synth'd?

  • Euk = 40s + 60s forms 80s (Even)
  • Prok = 30s + 50s forms 70s (Odd)

 

  • synth'd N terminus to C terminus

21

2nd step of protein synth?

+ its details

Initiation, Elongation, Termination

  • Think "going APE"
    • A site - binds incoming AA-tRNA
    • P site - accomodates growing peptide
    • E site - holds empty tRNA as it exits
  1. AA-tRNA binds A site (exc. initiator Met) using EF and GTP
  2. rRNA "ribozyme" catalyzes peptide bond formation, transfers polypept to AA on A site
  3. Ribosome advances 3 NTs toward 3' end mRNA, moving peptidyl tRNA to P site ("translocation")

22

3rd step of protein synth?

+ its details

Initiation, Elongation, Termination

  • "release factor" recognizes stop codon (UAG, UAA, UGA) + halts translation
  • completed polypept is released from ribosome, requiring GTP

23

What are the 2 types of PTMs?

+ 6 examples of 1 type

  1. Trimming - removing N- / C-terminal propeptides from zymogen > mature protein (eg trypsinogen > trypsin)
  2. Covalent Alterations - P-ation, glycosylation, OH-ation, methylation, acetylation, ubiquitination (PUGHAM)

24

What 3 processes does the Golgi perform on AAs / proteins in its function as a "distribution center" for proteins/lipids from ER to vesicles/membrane?

  1. Modifies Asn N-oligosaccharides
  2. Adds O-oligosacchs to Ser / Thr
  3. Adds mannose-6-phosphate to proteins for trafficking to lysosomes

25

What are endosomes?

"sorting centers" for material from outside cell or from Golgi

send stuff to lysosomes for destruction, or back to membrane/Golgi for use

26

What is I-cell disease?

Inclusion Cell Disease / Mucolipidosis Type II

  • inherited lysosomal N-acetylglucosaminyl-1-phosphotransferase defect
  • Golgi can't P-ate mannose resiudes on glycoproteins > proteins secreted EC rather than sent to lysosome
  • Clinical: coarse face, gingival hyp., cornea clouding, restricted joints, claw hand, kyphoscoliosis, high plasma lysosomal enzymes ... often fatal in childhood

27

What is the "signal recognition particle" ?

SRP is an abundant cytosolic ribonucleoprotein that traffics proteins from ribosome to RER

if dysfunctional/absent, proteins accumulate in cytosol

28

What are the 3 vesicular trafficking proteins + their functions?

"II steps forward, I steps back"

  1. COP-I - retrograde thru Golgi, cis-Golgi to ER
  2. COP-II - ER to cis-Golgi anterograde
  3. Clathrin - trans-Golgi to lysosome; membrane to endosomes (as in R-mediated endocytosis, such as LDL-Rs)

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