Studies of the changes in systemic copper metabolism and excretion produced by the intravenous administration of trithiomolybdate in sheep

Abstract

1. The effects of intravenous trithiomolybdate administration on the fate of 64Cu and on stable Cu metabolism were examined in sheep held in metabolism cages and fed on a low-Cu diet supplying 2.95 mg Cu/animal per d.2. In Expt 1 the injection of trithiomolybdate, 30 mg molybdenum/sheep per d for 5 d, greatly increased plasma Cu levels and more than doubled the faecal Cu excretion. Urinary Cu excretion was unaffected. The disappearance from plasma of 64Cu injected during the trithiomolybdate administration was slowed although faecal 64Cu excretion was increased more than threefold.3. In Expt 2 trithiomolybdate, 10 and 30 mg Mo/sheep per d for 3 d, was administered 22 h after the injection of 64Cu. Radioactivity reappeared immediately in plasma and faecal b 4 C~ excretion was increased.4. In both experiments the 64Cu and the increased stable Cu in plasma were associated with albumin. 5. The experiments explain the effectiveness of thiomolybdates as 'decoppering' agents and provide a model for some of the systemic effects seen in ruminants exposed to increased dietary Mo. The experiments support the view that the thiomolybdates, by causing the appearance of new ligands, alter the distribution of Cu in tissues and cause an overall depletion.

Unraveling the Role of Metal Ions and Low Catalytic Activity of Cytochrome C Oxidase in Alzheimer’s Disease

“…The increased ionic strength immediately slows down the interaction between COX and its substrate cytochrome c, (Wilms et al 1981) resulting in an accumulation of oxygen in the mitochondria. The excess oxygen promotes formation of oxygen radicals which damage the enzyme, the surrounding membrane and other mitochondrial proteins (Parker et al 1994b;Mason et al 1988). The damaged COX now turns over even more slowly causing more oxygen to accumulate and also causing potentially harmful oxygen radical intermediates to persist longer than usual (Zaslavsky et al 1999;Fabien and Palmer 2001) creating further opportunity for free radical damage to the enzyme and surrounding structures.…”

Effects of dietary copper, molybdenum and sulfur on biliary copper and zinc excretion in Simmental and Angus cattle

“…obs.). The origin of this extra plasma Cu, which we now believe contributes to the bile Cu pool, is not known precisely, but observations on sheep (Mason et al 1988;Gooneratne et al 1989a,b) or after TM4 administration (Gooneratne et al 198lb). …”

Impact of molybdenum on the copper status of red deer (Cervus elaphus)

“…The mechanism of the interaction between Cu, Mo and S is complex, the site of action being the reticulorumen, where sulphide ions (S 2-) from organic and inorganic sources, and molybdate ions (MoO 4 2-) react to from thiomolybdates, which then complex with Cu to from insoluble Cu thiomolybdates that are generally not absorbed but excreted in the faeces (Suttle 1974;Mason 1982;Mason et al 1984Mason et al , 1988. Some of these thiomolybdates, however, are absorbed and have an impact on tissue Cu levels.…”