Which of the following interfere with normal collagen formation or cross-linking?

A. Beta-aminopropionitrile.

B. Iron chelators.

C. Vitamin C depletion

D. Proline analogs (e.g., cis-hydroxyproline).

E. D-Penicillamine.

DISCUSSION: Intramolecular and intermolecular cross-links are crucial for collagen structural stability. Formation of cross-links can be inhibited by two pharmacologic agents: beta-aminopropionitrile inhibits the enzyme lysyl oxidase, and Dpenicillamine binds to collagen substrate directly to prevent collagen cross-link formation. Iron is a cofactor for prolyl hydroxylase, which is important for collagen synthesis. In high enough concentration, proline analogs prevent collagen formation with minimal effects on noncollagenase protein synthesis.