A 28-year-old woman presents with easy bruising, bleeding gums, and poor wound healing. Her serum vitamin C level is low. All of the following collagen abnormalities would be expected in scurvy EXCEPT:

Question

Accepted Answer

D. Impaired secretion of procollagen from the rough endoplasmic reticulum due to lack of signal peptide cleavage. ## Scurvy: Biochemical Basis of Collagen Defects

### Pathophysiology of Scurvy

**Key Point:** Vitamin C (ascorbic acid) is a cofactor for prolyl hydroxylase and lysyl hydroxylase. Without it, collagen cannot be properly hydroxylated, leading to structurally and functionally defective collagen [cite:Robbins 10e Ch 3].

### What DOES Go Wrong in Scurvy (Options 0, 1, 2)

**High-Yield:** The cascade of collagen defects:

1. **Defective hydroxylation (Option 0)** ✓ CORRECT
   - Prolyl hydroxylase and lysyl hydroxylase require vitamin C as a cofactor
   - Proline and lysine residues remain unhydroxylated
   - Hydroxyproline is essential for triple helix stability (extra H-bonding)

2. **Reduced cross-linking (Option 1)** ✓ CORRECT
   - Hydroxylysine residues are the substrate for lysyl oxidase
   - Without hydroxylation, fewer aldehydes (allysine) are formed
   - Fewer Schiff base and aldol cross-links result
   - Collagen becomes mechanically weak

3. **Abnormal triple helix geometry (Option 2)** ✓ CORRECT
   - Hydroxyproline stabilizes the triple helix through extra H-bonding
   - Without it, the helix is less stable and may have distorted geometry
   - The collagen may be synthesized but structurally compromised

### Why Option 3 Is Wrong

**Warning:** Procollagen signal peptide cleavage is **NOT** affected by vitamin C deficiency. This process is:
- Catalyzed by **signal peptidase** in the rough ER
- Independent of vitamin C
- A normal step in collagen synthesis that occurs regardless of hydroxylation status

**Clinical Pearl:** In scurvy, collagen is actually *synthesized* and *secreted* normally—the problem is that it is **structurally defective** once secreted. The signal peptide is cleaved normally; the defect lies in post-translational hydroxylation, which occurs *after* secretion in the rough ER and Golgi.

| Process | Vitamin C Requirement | Status in Scurvy |
| --- | --- | --- |
| Signal peptide cleavage | No | **Normal** |
| Prolyl hydroxylation | Yes | **Defective** |
| Lysyl hydroxylation | Yes | **Defective** |
| Triple helix formation | Indirect (depends on hydroxylation) | **Abnormal** |
| Secretion | No | **Normal** |
| Cross-linking | Yes (via hydroxylysine) | **Defective** |

Answer

A. Reduced covalent cross-linking between collagen molecules due to impaired lysyl oxidase function

Answer

B. Accumulation of collagen with normal amino acid composition but abnormal triple helix geometry

Answer

C. Defective hydroxylation of proline and lysine residues in the collagen backbone

A 28-year-old woman presents with easy bruising, bleeding gums, and poor wound healing. Her serum vitamin C level is low. All of the following collagen abnormalities would be expected in scurvy EXCEPT:

Explanation

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