PMID- 11082702 OWN - NLM STAT- MEDLINE DCOM- 20010215 LR - 20191210 IS - 0031-6903 (Print) IS - 0031-6903 (Linking) VI - 120 IP - 10 DP - 2000 Oct TI - [Biological regulation of copper and selective removal of copper: therapy for Wilson disease and its molecular mechanism]. PG - 899-908 AB - Copper (Cu) is an essential trace element and constitutes the active center of the redox Cu enzymes such as Cu, Zn-superoxide dismutase (Cu, Zn-SOD), ceruloplasmin and cytochrome c oxidase. Among hereditary diseases due to a defect in the metabolism of Cu, Menkes disease (caused by a Cu deficiency) and Wilson disease (caused by the excessive accumulation of Cu) have been shown to be caused by the mutation of genes encoding Cu-binding ATPase for the efflux of Cu, ATP7A and ATP7B, respectively. Following the identification of these causative genes, intracellular Cu transporters (Cu chaperones) specific for the Golgi apparatus, mitochondria and Cu, Zn-SOD were discovered, and these findings have facilitated the study of the underlying mechanisms of the biological regulation of Cu. Apart from these physiological and biochemical studies, toxicological studies have elucidated the underlying mechanisms of the occurrence of acute hepatitis caused by the accumulation of Cu accumulating in the liver of an animal model for Wilson disease, LEC rats. In these toxicological studies, two biological aspects of metallothionein (MT), i.e., antioxidant and prooxidant depending on the Cu/Zn ratio in Cu-containing MT have been proposed. The present article overviews the recent findings on the biological regulation of Cu and on the toxicological aspect of Cu. It is known that Cu forms a stable ternary complex with molybdenum and sulfur under reductive conditions in the body. On the basis of this observation, tetrathiomolybdate (TTM) has been applied to remove Cu from the liver of Long-Evans rats with a cinnamon-like coat color (LEC) rats. Precise mechanisms underlying the complex formation between Cu bound to MT and TTM were presented, and an appropriate protocol for the chelation therapy was also proposed together with the mechanisms underlying the occurrence of side-effects. FAU - Suzuki, K T AU - Suzuki KT AD - Faculty of Pharmaceutical Sciences, Chiba University, Japan. FAU - Ogura, Y AU - Ogura Y LA - jpn PT - Journal Article PT - Review PL - Japan TA - Yakugaku Zasshi JT - Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan JID - 0413613 RN - 0 (Carrier Proteins) RN - 0 (Cation Transport Proteins) RN - 0 (Chelating Agents) RN - 0 (Recombinant Fusion Proteins) RN - 789U1901C5 (Copper) RN - 81AH48963U (Molybdenum) RN - 9038-94-2 (Metallothionein) RN - 91U3TGV99T (tetrathiomolybdate) RN - EC 3.6.1.- (Adenosine Triphosphatases) RN - EC 7.2.2.8 (ATP7A protein, human) RN - EC 7.2.2.8 (ATP7B protein, human) RN - EC 7.2.2.8 (Atp7a protein, rat) RN - EC 7.2.2.8 (Copper-Transporting ATPases) SB - IM MH - Adenosine Triphosphatases MH - Animals MH - Carrier Proteins MH - *Cation Transport Proteins MH - Chelating Agents/therapeutic use MH - Copper/*metabolism MH - Copper-Transporting ATPases MH - Disease Models, Animal MH - Hepatolenticular Degeneration/metabolism/*therapy MH - Humans MH - Liver/metabolism MH - Metallothionein MH - Molybdenum/adverse effects/therapeutic use MH - Rats MH - Rats, Inbred LEC MH - *Recombinant Fusion Proteins RF - 96 EDAT- 2000/11/18 11:00 MHDA- 2001/03/03 10:01 CRDT- 2000/11/18 11:00 PHST- 2000/11/18 11:00 [pubmed] PHST- 2001/03/03 10:01 [medline] PHST- 2000/11/18 11:00 [entrez] AID - 10.1248/yakushi1947.120.10_899 [doi] PST - ppublish SO - Yakugaku Zasshi. 2000 Oct;120(10):899-908. doi: 10.1248/yakushi1947.120.10_899.