Effects of molybdate, sulfide, and tetrathiomolybdate on copper metabolism in rats

Tetrathiomolybdate anticopper therapy for Wilson's disease inhibits angiogenesis, fibrosis and inflammation

“…Molybdenum fed to ruminants, but not when fed to non-ruminants, was shown to cause copper deficiency [18][19][20]. Then it was realized that the sulfur-rich rumen was converting molybdenum to thiomolybdates [21], and these compounds were found to have anticopper activity in all animals, with the tetra-sulfur compound, TM, being the most potent [22][23][24].…”

“…However, all of its side effects in animals are due to copper deficiency, that is, copper supplementation prevents all TM toxicity [24]. TM acts as an anticopper agent by forming a tight tripartite complex with copper and protein [22][23][24][25]. Given with food, TM complexes food copper with food protein and prevents copper absorption [26][27][28][29].…”

Raulin award lecture: Wilson's disease therapy with zinc and tetrathiomolybdate

“…We placed patients on the regimen to be studied for several weeks before the study to allow complete washout of former therapies. With no therapy we saw an average of +0.25 mg/day positive copper balance and high absorption of orally administered 64 copper. A dose as low as 25 mg of zinc/day reduced the average positive balance significantly but did not consistently control copper balance or 64 copper uptake.…”

“…With no therapy we saw an average of +0.25 mg/day positive copper balance and high absorption of orally administered 64 copper. A dose as low as 25 mg of zinc/day reduced the average positive balance significantly but did not consistently control copper balance or 64 copper uptake. The same can be said for 25 mg × 2, 50 mg × 1 and 75 mg × 1.…”

“…As a geneticist, I was aware of Wilson's disease and the problems with penicillamine, and it occurred to me that perhaps we could develop zinc as a safer alternative. We then did copper balance and uptake studies with orally administered 64 copper in patients in whom we temporarily stopped penicillamine and treated with the same dose and regimen of zinc we had used for sickle cell anemia [19]. When these studies showed that zinc therapy produced a negative copper balance and blocked 64 copper absorption, we began the step-by-step development of zinc as a therapy in Wilson's disease [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35].…”