Mechanisms for protection against copper toxicity.
Essential transition metals such as copper, molybdenum, and zinc and nonessential metals like cadmium, mercury, and lead can be toxic at the cellular, tissue, and organ levels when present in excess. To avoid metal-induced toxicity most organisms use a redundant combination of metal-regulated import inhibition, sequestration, and enhanced export mechanisms. Combinations of these mechanisms are used to form detoxification pathways controlled through metal-binding proteins at transcriptional, translational, or enzymatic levels. In mammalian pathways copper is partially detoxified by sequestration in the metal-binding metallothioneins or export via the copper-translocating ATPases. Copper regulation of these two mechanisms is afforded by specific conformational changes induced in regulatory proteins on metal binding.
Dameron
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National Research Centre for Environmental Toxicology, Queensland, Coopers Plains, Australia. c.dameron@mailbox.uq.oz.au
Harrison
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D000251:Adenosine Triphosphatases / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D027682:Cation Transport Proteins; D003300:Copper / Q000009:adverse effects* / Q000493:pharmacokinetics*; D000073840:Copper-Transporting ATPases; D006801:Humans; D008658:Inactivation, Metabolic; D008668:Metallothionein / Q000502:physiology*; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins; D015533:Transcriptional Activation
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D011993:Recombinant Fusion Proteins; D003300:Copper; D008668:Metallothionein; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases