Usmle - Biochem 4/4

Front 1

What enzyme is responsible for transcribing:

Eukaryotic rRNA?
Eukaryotic mRNA?
Eukaryotic tRNA?

Back 1

rRNA: RNA Polymerase I

mRNA: RNA Polymerase II

tRNA: RNA Polymerase III

Front 2

List and describe the various permutations of RNA, IN ORDER, en route to the mature transcript.

Back 2

1) Heterogenous nuclear RNA (hnNRA)
-- completely unprocessed.
-- if it's destined for translation, it's called pre-mRNA

2) mRNA
-- transcript that's been capped, tailed, and spliced *IN THE NUCLEUS*

Front 3

What is the polyadenylation signal?

Back 3

AAUAA

This RNA sequence signals that for the poly-A tail to be attached here by poly-A polymerase.

Front 4

What is the polyadenylation signal?

Back 4

AAUAAA

This RNA sequence signals that for the poly-A tail to be attached here by poly-A polymerase.

Front 5

Splice mechanism, quick and dirty:

Back 5

1. snRNP's bind primary transcript at splicing sites (marked at either end by GU and AG sequences)

2. snRNP's form a spliceosome, there, and fold the intron into a lariat (loop)

3. Splice!

Hint 5

snRNP's = small nuclear ribonucleoproteins.

Front 6

How does lupus interfere with production of mature mRNA?

Back 6

Patients with lupus often make antibodies to spliceosomal snRNP's, disrupting splicing.

Front 7

How do the presence of glucose and lactose affect gene transcription in e. coli?

Back 7

This sugar binds a repressor protein, interfering with its constitutive binding to the promoter sequence of the lac operon.

Hint 7

The presence of this sugar inhibits the activator of the lac operon, the CAP protein, from binding to the lac operon promoter.

It does so indirectly, by downregulating cAMP presence in the cell, which is necessary for CAP's activating behavior.

Front 8

What sequence is at the 3' end of tRNA, and why does this matter?

Back 8

CCA: found at the 3' end of tRNA. The amino acid binds at this end.

CCA: Can Carry Amino acids

Front 9

What drug interferes with the interaction between amino-acyl tRNA and the 30S ribosomal subunit?

Back 9

Tetracyclines attack these proteins specific to bacteria.

Front 10

List the drugs that bind the 30S subunit of bacterial ribosomes to prevent mRNA translation. How do they do so?

Back 10

1) Aminoglycosides bind 30S ribosomal subunit, preventing initiation.

2) Tetracyclines bind the 30S ribosomal subunit, blocking access of charged tRNA's to the ribosomal subunit.

Hint 10

Aminoglycosides: Streptomycin, Amikacin

Tetracyclines: demeclocycline, doxycycline

Front 11

(1) List the toxins that interfere with protein translation in humans. (2) How do they do so?

Back 11

1. Shiga toxin
2. Shiga-like toxin (made by EHEC)
3. Diphtheria toxin

Hint 11

1. This toxin behaves just like tetracycline but in eukaryotes, preventing the binding of charged tRNA to the ribosomal complex.

2. Almost the same toxin is made by enterohemorrhagic E. coli.

3. This toxin inactivates EF-2, preventing the translocation step of protein translation in eukaryotes; the ribosome cannot move down the transcript.

Front 12

What are the major proteins associated with the major steps of protein translation?

Back 12

1. Initiation: IF's

2. Elongation & Translocation: EF's

3. Termination: RF's (release factors)

Front 13

Distinguish Translocation and Elongation in protein translation.

Back 13

Elongation refers to the new peptide bond that's formed.

Translocation refers to the movement of the ribosome down the mRNA transcript to the next codon (in the 3' direction)

Front 14

Ribosomal binding sites:

Back 14

A site: Activation site, where aminoacyl-tRNA first bind

P: site of Peptide elongation

E: Exit site, site of termination

APE

Front 15

List the drugs that bind the 50S ribosomal subunit.

Back 15

Macrolides bind the 50S subunit, preventing ribosomal translocation and halting protein translation.

Clindamycin does the same thing.

Chloramphenicol binds the 50S subunit, but it prevents *elongation.

Hint 15

Macrolides: erythromycin, azithromycin, etc.

Chloramphenicol and Clinda are synthetic antibiotics, and are in their own classes.

Clindamycin causes C diff
Chloramphenicol is cheap!

Front 16

Biochemical role of Mannose-6-phosphate

Back 16

This sugar is added to lysozomal enzymes while still in the Golgi apparatus, marking them for shipment to the lysozomes.

Front 17

List the main vesicular coating compounds and their corresponding destinations.

Back 17

1. COPI: Retrograde transport from Golgi back to ER

2. COPII: anterograde transport from ER to cis-Golgi

3. Clathrin: transport from trans-Golgi to surface membrane

Front 18

I-cell Disease / Mucolipidosis II
Path & Presentation:

Back 18

Lysozomal storage disorder in which inability to add mannose-6-phosphate to lysozomal enzymes results in their being secreted into the extracellular space.

This lysozomal storage disorder looks like MPS but is characterized by inability to transport many different lysozomal enzymes rather than an inability to make a certain lysozomal enzyme.

Hint 18

Presentation: coarse facial features, clouded corneas, restricted joint movement, hi plasma levels of lysozomal enzymes. Often fatal in childhood.

Front 19

List the 5 drugs that act on microtubules.

Back 19

1. Mebendazole/thiabendazole
(antihelminic)

2. Griseofulvin
(antifungal)

3. Vincristine/vinblastine

4. Paclitaxel
(anti-breast cancer)

5. Colchicine
(anti-gout)

Front 20

Kartagener's Syndrome
Path & Presentation

Back 20

Immotile cilia d/t a dynein arm defect.
(dynein arm

Hint 20

Infertility, sinusitis, bronchiectases

Also associated with situs inversus

Front 21

How do cilia move?

Back 21

Made of microtubules with dynein and kinesin arms attaching each to a neighboring microtubule.

Dynein: walks away from the base of the cilia (retrograde)

Kinesin: walks toward center of cilia (anterograde).

Front 22

Chediak-Higashi syndrome
Path & Presentation

Back 22

Recessive mutation to MAP proteins.

MAP proteins stabilize microtubules, preventing "catastrophe".

Simply put, its a defect in microtubular polymerization that results in decreased organelle and granule transportation, especially in:

Neutrophils
Lymphocytes
Melanocytes

Hint 22

A child presents with:

1. oculocutaneous albinism (white hair, red eyes)

2. frequent pyogenic infections.

Front 23

Describe cilia's biochem.

Back 23

9 + 2 microtubule arrangement

9 microtubule doublets form a circle around a central doublet.

Axonemal Dynein links the peripheral doublets together so they move in concert.