Investigations into the antagonism of copper metabolism by molybdenum and sulphur in the sheep and the rat

An investigation was made of the role of thiomolybdates as intermediates in the antagonistic effects of Mo and S on Cu metabolism in sheep. The effects of tetrathiomolybdate (TIM) on the distribution of Cu amongst liver proteins, and on the metabolism of plasma albumin was examined in more detail in rats. In rumen contents, approximately 88% of the Cu and 94% of the Mo was associated with the solid phase that consisted of plant material and adhering microorganisms. When ammonium molybdate (AM) or TTM at concentrations between 5 and 25 ug Mo/g was introduced in vivo or in vitro, the proportion of Cu and Mo in the solid phase was increased at the expense of the proportion in the fluid phase, and less of the Cu was soluble in 5% trichloroacetic acid and neutral detergent. Column chromatography revealed that both Cu and Mo was associated with compounds of high molecular weight that were most likely to be proteins. It was confirmed that TTM administered orally induced similar qualitative changes in tissue Cu concentrations, atomic ratios of Cu:Mo and the activity of Cu-dependent enzymes as did equivalent amounts of AM. A comparison was made between the effects of TTM and two molybdo-amino acids (cysteine-Mo, cysteine-Mo-S) administered intravenously, in order to explore the possibility that TIM acts via the formation of these compounds. Cysteine-Mo-S caused some of the systemic effects of TTM but cysteine-Mo was without significant effect. Studies with rats established that TIM interacted with high molecular weight proteins in the liver to form molybdo-proteins that were capable of removing Cu from metallothionein. Exposure of albumin to TTM resulted in a product that was more resistant to degradation in the kidney. Taken together, the results support the concept that thiomolybdates are intermediaries in the interaction between Cu, Mo and S in ruminants. It is postulated that thiomolybdates associate with proteins in the gastrointestinal tract and body tissues to form molybdo-proteins that bind Cu strongly and thereby decrease Cu absorption, as well as the availability of Cu for normal metabolism in the animal