title: Tetrathiomolybdate causes formation of hepatic copper-molybdenum clusters in an animal model of Wilson's disease.
abstract: Wilson's disease is an autosomal recessive human illness in which large quantities of copper accumulate in various organs, including the brain and the liver. If left untreated, it results in hepatitis, neurological complications, and death. Long-Evans Cinnamon (LEC) rats have a homologous mutation to Wilson's disease and thus provide an animal model. Liver lysosomes from tetrathiomolybdate-treated LEC rats were isolated and analyzed by Cu and Mo K-edge X-ray absorption spectroscopy. The lysosomes contained a Cu-Mo-S cluster in which the Mo is coordinated by four sulfurs at 2.24 A with approximately three copper neighbors at 2.70 A. Each Cu is coordinated to 3-4 sulfurs at 2.28 A with approximately one Mo neighbor at 2.70 A. These results indicate the formation of a biologically novel molybdenum-copper-sulfur cluster.
authors.affiliation: Stanford Synchrotron Radiation Laboratory, Stanford Linear Accelerator Center, 2575 Sand Hill Road, MS 69, Menlo Park, California 94025, USA. g.george@stanford.edu
authors.forename: Graham N
authors.initials: GN
authors.lastname: George
authors.forename: Ingrid J
authors.initials: IJ
authors.lastname: Pickering
authors.forename: Hugh H
authors.initials: HH
authors.lastname: Harris
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gailer
authors.forename: Dominik
authors.initials: D
authors.lastname: Klein
authors.forename: Josef
authors.initials: J
authors.lastname: Lichtmannegger
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Summer
mesh_terms: D000818:Animals; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D004195:Disease Models, Animal; D005583:Fourier Analysis; D006527:Hepatolenticular Degeneration / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D008982:Molybdenum / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D020332:Rats, Inbred LEC; D013052:Spectrometry, X-Ray Emission / Q000379:methods; D013455:Sulfur / Q000737:chemistry / Q000378:metabolism
chemical_list: D013455:Sulfur; D003300:Copper; D008982:Molybdenum; C020809:tetrathiomolybdate