A researcher is tracing the fate of C-peptide, a product of preproinsulin cleavage. Which of the following is a true statement regarding the fate of C-peptide?

C-peptide is packaged with insulin in secretory vesicles

C-peptide exits the cells via a protein channel

C-peptide is further cleaved into insulin

C-peptide is immediately degraded by the proteasome

C-peptide activates an intracellular signaling cascade

An 18-year old college freshman presents to his university clinic because he has not been feeling well for the past two weeks. He has had a persistent headache, occasional cough, and chills without rigors. The patient’s vital signs are normal and physical exam is unremarkable. His radiograph shows patchy interstitial lung infiltrates and he is diagnosed with atypical pneumonia. The patient is prescribed azithromycin and takes his medication as instructed. Despite adherence to his drug regimen, he returns to the clinic one week later because his symptoms have not improved. The organism responsible for this infection is likely resistant to azithromycin through which mechanism?

Methylation of ribosomal binding site

Decreased binding to RNA polymerase

An investigator is studying the genotypes of wingless fruit flies using full exome sequencing. Compared to wild-type winged fruit flies, the wingless fruit flies are found to have a point mutation in the gene encoding wing bud formation during embryogenesis. The point mutation in the gene causes the mRNA transcript to have a 'UUG' segment instead of an 'AUG' segment. Which of the following processes is most likely affected by this mutation?

Binding of met-tRNA to 40S complex

Catalyzation of peptide bond formation

Dissociation of mRNA from ribosome complex

Shift of peptidyl-tRNA from A to P site

You are treating a neonate with meningitis using ampicillin and a second antibiotic, X, that is known to cause ototoxicity. What is the mechanism of antibiotic X?

It binds the 30S ribosomal subunit and inhibits formation of the initiation complex

It binds the 50S ribosomal subunit and inhibits formation of the initiation complex

It binds the 30S ribosomal subunit and reversibly inhibits translocation

It binds the 50S ribosomal subunit and inhibits peptidyltransferase

It binds the 50S ribosomal subunit and reversibly inhibits translocation

A 70-year-old man with loose stools over the last 24 hours, accompanied by abdominal pain, cramps, nausea, and anorexia, was hospitalized. Previously, the man was diagnosed with a lung abscess and was treated with clindamycin for 5 days. Past medical history was significant for non-erosive antral gastritis and hypertension. He takes esomeprazole and losartan. Despite the respiratory improvement, fevers and leukocytosis persisted. Which of the following pathogenic mechanisms would you expect to find in this patient?

Glucosylation of Rho family GTPases

Inactivation of elongation factor EF-2

Inactivation of the 60S ribosome subunit

Cell membrane degradation by lecithinase

ADP-ribosylation of Gs-alpha subunit of G-protein coupled receptors

A 12-year-old male presents to the emergency department following several days of facial edema. A urinalysis confirms proteinuria and hematuria. Once admitted, a kidney biopsy is viewed under an electron microscope to confirm the diagnosis of minimal change disease. In the following electron micrograph, what process occurs in the structure marked with an arrow?

Podocyte foot process effacement

Normal podocyte foot process interdigitation

Glomerular basement membrane thickening

Elongation and termination of translation for USMLE Step 2 CK: High-Yield Biochemistry Lessons

Elongation Cycle - The Ribosome's Rhythm

Goal: Add amino acids to the growing polypeptide chain, guided by the mRNA template.
Energy: Requires GTP hydrolysis for tRNA binding and translocation.
Sites: 📌 Mnemonic: A for Aminoacyl-tRNA Arrival, P for Peptidyl-tRNA, E for Exit.

Ribosome elongation cycle with A, P, and E sites

Termination:

When a stop codon (UAA, UAG, UGA) enters the A site, Release Factors (RFs) bind.
The completed polypeptide is hydrolyzed from the P-site tRNA.

⭐ Macrolide antibiotics (e.g., Azithromycin) bind to the 50S ribosomal subunit and block the translocation step, inhibiting prokaryotic protein synthesis.

Elongation Factors - GTP's Grand Push

Elongation Cycle: A GTP-powered, three-step process that adds amino acids to the growing polypeptide chain.

Key Factors:
- Prokaryotes: EF-Tu (tRNA delivery), EF-G (translocation).
- Eukaryotes: eEF-1A (tRNA delivery), eEF-2 (translocation).
- 📌 Mnemonic: Tu/1A brings tRNA to the A-site; G/2 helps it go.
Termination: Stop codons (UAA, UAG, UGA) recruit Release Factors (RFs) to the A-site, triggering hydrolysis and release of the polypeptide.

⭐ Diphtheria toxin and Pseudomonas Exotoxin A inhibit protein synthesis by inactivating eEF-2 through ADP-ribosylation.

Termination - The Final Full Stop

Process initiated when a stop codon (UAA, UAG, UGA) enters the ribosomal A site.
Eukaryotic releasing factors (eRFs) are key:
- eRF1: Recognizes all three stop codons.
- eRF3: A GTPase that helps eRF1 bind and promotes cleavage.
Binding of eRFs triggers hydrolysis of the bond linking the polypeptide to the tRNA in the P site.

⭐ U Are Away, U Are Gone, U Go Away - The three stop codons signal termination.

Ribosome with RF1 binding to P-tRNA and mRNA

Translation Inhibitors - Antibiotic Ambush

📌 Mnemonic: "Buy AT 30, CCEL at 50"

30S Subunit Inhibitors:
- Aminoglycosides (e.g., Gentamicin, Tobramycin)
  - Irreversibly bind to 30S, block initiation complex formation, cause misreading of mRNA.
- Tetracyclines (e.g., Doxycycline)
  - Bind to 30S, prevent aminoacyl-tRNA from binding to the A-site.
50S Subunit Inhibitors:
- Chloramphenicol
  - Binds to 50S, inhibits peptidyltransferase.
- Clindamycin & Erythromycin (Macrolides)
  - Bind to 50S, block translocation (movement of ribosome along mRNA).
- Linezolid
  - Binds to 50S, prevents formation of the initiation complex.

⭐ Diphtheria toxin and Pseudomonas aeruginosa Exotoxin A inactivate eukaryotic Elongation Factor 2 (eEF-2) via ADP-ribosylation, halting human protein synthesis.

Antibiotic mechanisms on bacterial ribosome translation

High‑Yield Points - ⚡ Biggest Takeaways

Elongation requires GTP hydrolysis for aminoacyl-tRNA binding to the A site and for the translocation of the ribosome along the mRNA.

The large ribosomal subunit's rRNA acts as a ribozyme (peptidyltransferase) to catalyze peptide bond formation.

Termination occurs when a stop codon (UAA, UAG, UGA) enters the A site.

Release factors bind to the stop codon, promoting hydrolysis of the polypeptide from the tRNA.

Continue reading on Oncourse

CONTINUE READING — FREE

or get the app

App Store|Google Play