A Defect in the Intramolecular and Intermolecular Cross-linking of Collagen Caused by Penicillamine

Abstract

Abstract The administration of penicillamine to rats causes an accumulation of soluble collagen in soft tissues. The preponderance of α components in the tropocollagen subunits isolated indicates a lack of intramolecular cross-links, while the marked solubility of the collagen fibers in 0.5 m NaCl reflects the absence of covalent intermolecular bonds. Penicillamine does not affect the rate of synthesis of tropocollagen, but blocks almost quantitatively the formation of new insoluble collagen. In addition, it accelerates the turnover of the pre-existing insoluble material by presumably cleaving intermolecular bonds, which stabilize the fibrous structure. It will inhibit or retard fibrillogenesis in vitro, or cause a redissolution of the formed fibers upon cooling, depending on its concentration in the medium.