Q.17 Lysozyme cleaves peptidoglycan at

(1) N-acetyl muramic acid and N-acetyl glucosamine

(2) N-acetyl glucosamine and N-acetyl muramic acid

(3) N-acetyl muramic acid and N-acetyl muramic acid

(4) N-acetyl glucosamine and N-acetyl glucosamine

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Lysozyme’s Role in Bacterial Cell Wall Destruction

Lysozyme, also called muramidase, is a key antimicrobial enzyme found in tears, saliva, and egg whites. It targets peptidoglycan—the rigid mesh in Gram-positive bacterial cell walls—by hydrolyzing specific glycosidic bonds. This MCQ nails a core biochemistry concept: Lysozyme cleaves peptidoglycan at (1) N-acetyl muramic acid and N-acetyl glucosamine (2) N-acetyl glucosamine and N-acetyl muramic acid (3) N-acetyl muramic acid and N-acetyl muramic acid (4) N-acetyl glucosamine and N-acetyl glucosamine.

Correct Answer: (2) N-acetyl glucosamine and N-acetyl muramic acid

Lysozyme specifically attacks the β-1,4 glycosidic linkage between these sugars.

Mechanism: How Lysozyme Hydrolyzes the NAG-NAM Bond

Peptidoglycan consists of repeating N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) units, cross-linked by peptides. Lysozyme’s active site features Glu35 and Asp52 residues:

1. NAG binds first, distorting the sugar ring into a half-chair conformation.

2. Glu35 acts as a general acid, protonating the oxygen in the β-1,4 bond between NAG (carbon 1) and NAM (carbon 4).

3. Asp52 stabilizes the oxocarbenium ion intermediate.

4. Water attacks, cleaving the bond and forming new hydroxyl groups.

This weakens the cell wall, causing lysis—crucial for innate immunity. Crystal structures (e.g., Phillips 1967) confirm specificity for the NAG-(β1→4)-NAM bond.

Explanation of All Options: Spot the Difference

Options test bond specificity. Here’s why only one is right:

• (1) N-acetyl muramic acid and N-acetyl glucosamine: Incorrect order. This reverses the cleavage site (NAM to NAG), which lysozyme doesn’t target—peptidoglycan chains run NAG-NAM-NAG-NAM.

• (2) N-acetyl glucosamine and N-acetyl muramic acid: Correct. Precisely describes the hydrolyzed β-1,4 linkage from NAG’s C1 to NAM’s C4.

• (3) N-acetyl muramic acid and N-acetyl muramic acid: Incorrect. NAM-NAM bonds don’t exist; peptidoglycan alternates NAG-NAM.

• (4) N-acetyl glucosamine and N-acetyl glucosamine: Incorrect. NAG-NAG linkages aren’t present or targeted.

Broader Implications in Microbiology and Immunity

Understanding lysozyme cleaves peptidoglycan at NAG-NAM bonds explains antibiotic synergy (e.g., with penicillin) and resistance in Gram-negatives (outer membrane blocks access). For your studies, visualize via this simplified structure:

$\text{NAG}-(\beta 1\to 4)-\text{NAM}-(\beta 1\to 4)-\text{NAG}$

Key resource: Voet & Voet Biochemistry or PDB entry 2LZM for 3D models.