title: Cadmium ions inhibit procollagen C-proteinase and cupric ions inhibit procollagen N-proteinase.
abstract: Procollagen C- and N-proteinases specifically cleave the C- and N-terminal extension propeptides of type I, II and III procollagen molecules. The collagen molecules generated by the enzymes self-assemble into collagen fibrils. We previously observed the inhibition of these enzymes purified from chick tendons by several divalent metals. Here the inhibitory effects of CdCl2, CuCl2, ZnCl2, NiCl2, CoCl2 and Hg(C2H3O2)2 have been studied in detail using crude or purified C- and N-proteinases from chick tendons and sterna. CdCl2 was a strong inhibitor of C-proteinases from both sources, and the inhibition was independent of enzyme purity (I50 = 10-16 microM). In contrast, CuCl2 and ZnCl2 were inhibitory only of purified C-proteinase. With the N-proteinase, CuCl2 was a strong inhibitor, and the inhibition was independent of the purity of the enzyme preparation used (I50 = 14-40 microM). On the other hand, CdCl2 was a moderate inhibitor, and ZnCl2 was a strong inhibitor only of the purified N-proteinase (I50 = 8-17 microM). NiCl2 inhibited crude and purified N-proteinase from sternum (I50 = 23-29 microM) but not from tendon. These results suggest, therefore, that the accumulation of some of these metals in the body may cause suppression of collagen fibril formation in tissues.
authors.affiliation: Department of Biochemistry and Molecular Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Y
authors.initials: Y
authors.lastname: Hojima
authors.forename: B
authors.initials: B
authors.lastname: Behta
authors.forename: A M
authors.initials: AM
authors.lastname: Romanic
authors.forename: D J
authors.initials: DJ
authors.lastname: Prockop
mesh_terms: D000818:Animals; D055395:Bone Morphogenetic Protein 1; D019485:Bone Morphogenetic Proteins; D001842:Bone and Bones / Q000201:enzymology; D002104:Cadmium / Q000494:pharmacology*; D019256:Cadmium Chloride; D002642:Chick Embryo; D002712:Chlorides / Q000494:pharmacology*; D003035:Cobalt / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D010450:Endopeptidases / Q000378:metabolism; D007700:Kinetics; D008628:Mercury / Q000494:pharmacology; D008666:Metalloendopeptidases; D009532:Nickel / Q000494:pharmacology; D011348:Procollagen N-Endopeptidase / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000494:pharmacology*; D013249:Sternum; D013710:Tendons / Q000201:enzymology; D017967:Zinc Compounds / Q000494:pharmacology
chemical_list: D019485:Bone Morphogenetic Proteins; D002712:Chlorides; D011480:Protease Inhibitors; D017967:Zinc Compounds; D002104:Cadmium; D003035:Cobalt; C022838:nickel chloride; D003300:Copper; D009532:Nickel; C016837:zinc chloride; D010450:Endopeptidases; D008666:Metalloendopeptidases; D011348:Procollagen N-Endopeptidase; D055395:Bone Morphogenetic Protein 1; C018021:cobaltous chloride; D008628:Mercury; D019256:Cadmium Chloride; C029823:mercuric acetate; C029892:cupric chloride