Cadmium ions inhibit procollagen C-proteinase and cupric ions inhibit procollagen N-proteinase. 1994

Y Hojima, and B Behta, and A M Romanic, and D J Prockop
Department of Biochemistry and Molecular Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.

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.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008628 Mercury A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to MERCURY POISONING. Because of its toxicity, the clinical use of mercury and mercurials is diminishing.
D008666 Metalloendopeptidases ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism. Metallo-Endoproteinases,Metalloendopeptidase
D009532 Nickel A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme UREASE.
D010450 Endopeptidases A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS. Endopeptidase,Peptide Peptidohydrolases
D011348 Procollagen N-Endopeptidase An extracellular endopeptidase which excises a block of peptides at the amino terminal, nonhelical region of the procollagen molecule with the formation of collagen. Absence or deficiency of the enzyme causes accumulation of procollagen which results in the inherited connective tissue disorder--dermatosparaxis. EC 3.4.24.14. Procollagen Peptidase,Procollagen N-Proteinase,Procollagen N Endopeptidase,Procollagen N Proteinase
D011480 Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES). Antiprotease,Endopeptidase Inhibitor,Endopeptidase Inhibitors,Peptidase Inhibitor,Peptidase Inhibitors,Peptide Hydrolase Inhibitor,Peptide Hydrolase Inhibitors,Peptide Peptidohydrolase Inhibitor,Peptide Peptidohydrolase Inhibitors,Protease Antagonist,Protease Antagonists,Antiproteases,Protease Inhibitor,Antagonist, Protease,Antagonists, Protease,Hydrolase Inhibitor, Peptide,Hydrolase Inhibitors, Peptide,Inhibitor, Endopeptidase,Inhibitor, Peptidase,Inhibitor, Peptide Hydrolase,Inhibitor, Peptide Peptidohydrolase,Inhibitor, Protease,Inhibitors, Endopeptidase,Inhibitors, Peptidase,Inhibitors, Peptide Hydrolase,Inhibitors, Peptide Peptidohydrolase,Inhibitors, Protease,Peptidohydrolase Inhibitor, Peptide,Peptidohydrolase Inhibitors, Peptide
D001842 Bone and Bones A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principal cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX. Bone Tissue,Bone and Bone,Bone,Bones,Bones and Bone,Bones and Bone Tissue,Bony Apophyses,Bony Apophysis,Condyle,Apophyses, Bony,Apophysis, Bony,Bone Tissues,Condyles,Tissue, Bone,Tissues, Bone
D002104 Cadmium An element with atomic symbol Cd, atomic number 48, and atomic weight 112.41. It is a metal and ingestion will lead to CADMIUM POISONING.
D002642 Chick Embryo The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching. Embryo, Chick,Chick Embryos,Embryos, Chick

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