Ruminants are more vulnerable to
copper deficiency than humans because rumen
sulfide generation lowers
copper availability from forage, increasing the risk of conditions such as
swayback in lambs.
Molybdenum-rich pastures promote
thiomolybdate (TM) synthesis and formation of unabsorbable Cu-TM complexes, turning risk to clinical reality (hypocuprosis). Selection pressures created ruminant species with tolerance of deficiency but vulnerability to
copper toxicity in alien environments, such as specific pathogen-free units. By contrast, cases of
copper imbalance in humans seemed confined to rare genetic aberrations of
copper metabolism. Recent descriptions of human
swayback and the exploratory use of TM for the treatment of
Wilson's disease,
tumor growth, inflammatory diseases, and
Alzheimer's disease have created unexpected common ground. The incidence of pre-hemolytic
copper poisoning in specific pathogen-free lambs was reduced by an
infection with Mycobacterium avium that left them more responsive to treatment with TM but vulnerable to long-term
copper depletion.
Copper requirements in ruminants and humans may need an extra allowance for the "
copper cost" of immunity to
infection. Residual cuproenzyme inhibition in TM-treated lambs and anomalies in plasma
copper composition that appeared to depend on liver
copper status raise this question "can chelating capacity be harnessed without inducing
copper-deficiency in ruminants or humans?" A model of equilibria between exogenous (TM) and endogenous
chelators (e.g.,
albumin,
metallothionein) is used to predict risk of exposure and hypocuprosis; although risk of natural exposure in humans is remote, vulnerability to TM-induced
copper deficiency may be high.
Biomarkers of TM impact are needed, and
copper chaperones for inhibited cuproenzymes are prime candidates.