Inhibitors of Translation
Inhibitors of Translation - OMPATH
# **Inhibitors of Translation**
Translation inhibitors are mostly **antibiotics** that target bacterial ribosomes. Since **bacteria rely heavily on protein synthesis**, these drugs disrupt translation and prevent bacterial growth.
## **Differences Between Prokaryotic and Eukaryotic Ribosomes**
- **Prokaryotic ribosomes**: **70S**, composed of **30S (small subunit) and 50S (large subunit)**.
- **Eukaryotic ribosomes**: **80S**, composed of **40S (small subunit) and 60S (large subunit)**.
Most antibiotics **target the differences** between bacterial (prokaryotic) and human (eukaryotic) ribosomes to avoid harming human cells.
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# **Differences Between Translation in Prokaryotes and Eukaryotes**
# **Categories of Translation Inhibitors (Antibiotics)**
### **1. Aminoglycosides**
- **Mechanism**:Bind to **both 30S and 50S ribosomal subunits**.
- **Block codon recognition**, preventing translation.
- Cause **misreading of mRNA**, leading to defective proteins.
- **Examples**:**Streptomycin**, **Gentamicin**, **Kanamycin**.
- **Toxicity & Side Effects**:**Ototoxicity (hearing loss)** – damages the ear.
- **Nephrotoxicity (kidney damage)** – inhibits prostaglandins (vasodilators).
- **Vestibular damage** – causes dizziness.
- **Resistance Mechanisms**:Ribosomal **mutations** preventing drug binding.
- Enzymatic modification of the drug (**phosphorylation**).
- **Efflux pumps** remove the drug from bacteria.
### **2. Tetracyclines**
- **Mechanism**:Bind to **30S ribosomal subunit**.
- **Block tRNA binding** to mRNA, preventing elongation.
- **Examples**:**Doxycycline**, **Oxytetracycline**, **Chlorotetracycline**.
- **Toxicity & Side Effects**:**Photosensitivity** – avoid sun exposure.
- **Teeth discoloration** – **should not be given to children**.
- **Gastrointestinal distress**.
- **Resistance Mechanisms**:**Efflux pumps** remove the drug from bacterial cells.
- **Mutations** in ribosomal binding sites.
- **Plasmid-coded resistance genes**.
### **3. Macrolides**
- **Mechanism**:Bind to **50S ribosomal subunit**.
- **Prevent mRNA movement** between the **A-site and P-site**, stopping elongation.
- **Examples**:**Erythromycin**, **Clarithromycin**, **Azithromycin**.
- **Toxicity & Side Effects**:**Gastrointestinal (GIT) disturbances**.
- **Metallic taste**.
- **Resistance Mechanisms**:**Methylation of 50S ribosomal subunit**, preventing drug binding.
- **Efflux pumps** remove the drug from the cell (plasmid-mediated).
### **4. Chloramphenicol**
- **Mechanism**:Binds to **50S ribosomal subunit**.
- **Inhibits peptide bond formation**, stopping protein synthesis.
- **Toxicity & Side Effects**:**Bone marrow suppression** – can lead to **aplastic anemia**.
- **Mitochondrial damage** – causes toxicity in human cells.
- **Resistance Mechanisms**:Bacteria produce **enzymes that modify chloramphenicol**, preventing its action.
# **Short-Answer Questions and Answers**
### **1. Discuss in detail the mechanisms, actions, toxicity, and effects of translation-inhibiting drugs.**
**Answer:**
- **Aminoglycosides** bind **both ribosomal subunits**, interfere with **codon recognition**, and cause **misreading of mRNA**. They are **bactericidal** but cause **renal and ear toxicity**.
- **Tetracyclines** bind to **30S**, block **tRNA attachment**, and prevent **elongation**. They cause **teeth discoloration** and **photosensitivity**.
- **Macrolides** bind **50S**, block **mRNA movement**, and prevent **elongation**. They cause **GIT issues** and **metallic taste**.
- **Chloramphenicol** binds **50S**, blocks **peptide bond formation**, but has **high toxicity (anemia, mitochondrial damage)**.
### **2. Differentiate between translation in prokaryotes and eukaryotes. (10 marks)**
**Answer:**
### **3. Differentiate between translation and transcription. (10 marks)**
**Answer:**
**10 key points** differentiating **transcription** and **translation**:
### **Transcription vs. Translation (10 Points)**
## **Recombinant DNA Technology & Cloning**
Recombinant DNA technology, also known as **genetic engineering**, involves modifying genetic material to create new combinations of DNA. This technology was developed in the **1970s** after the discovery of **restriction enzymes** in bacteria.
### **Key Components of Recombinant DNA Technology**
- **Restriction Enzymes**Found in bacteria.
- Function: Cut DNA at specific **restriction sites** (also called **palindromic sequences**).
- Example: **EcoRI (from Escherichia coli)** recognizes **5' AATTC 3'** and cuts at this site.
- Produces either:**Sticky ends** (cohesive, easier for DNA recombination).
- **Blunt ends** (straight cuts).
- **Plasmids (Vectors)****Small, circular, extra-chromosomal DNA** in bacteria.
- Self-replicating, used to **carry foreign DNA** into host cells.
- Contains:**Origin of replication (Ori)** – ensures self-replication.
- **Antibiotic resistance gene** – helps in selecting transformed cells.
- **Multiple cloning site (M