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Abstract

Iron and copper are metals which play an important role in the living world. From a brief consideration of their chemistry and biochemistry we conclude that the early chemistry of life used water soluble ferrous iron while copper was in the water-insoluble Cu(I) state as highly insoluble sulphides. The advent of oxygen was a catastrophic event for most living organisms, and can be considered to be the first general irreversible pollution of the earth. In contrast to the oxidation of iron and its loss of bioavailability as insoluble Fe(III), the oxidation of insoluble Cu(I) led to soluble Cu(II). A new iron biochemistry became possible after the advent of oxygen, with the development of chelators of Fe(III), which rendered iron once again accessible, and with the control of the potential toxicity of iron by its storage in a water soluble, non-toxic, bio-available storage protein (ferritin). Biology also discovered that whereas enzymes involved in anaerobic metabolism were designed to operate in the lower portion of the redox spectrum, the arrival of dioxygen created the need for a new redox active metal which could attain higher redox potentials. Copper, now bioavailable, was ideally suited to exploit the oxidizing power of dioxygen. The arrival of copper also coincided with the development of multicellular organisms which had extracellular cross-linked matrices capable of resisting attack by oxygen free radicals. After the initial 'iron age' subsequent evolution moved, not towards a 'copper age', but rather to an 'iron-copper' age. In the second part of the review, this symbiosis of iron and copper is examined in yeast. We then briefly consider iron and copper metabolism in mammals, before looking at iron-copper interactions in mammals, particularly man, and conclude with the reflection that, as in Greek and Roman mythology, a better understanding of the potentially positive interactions between Mars (iron) and Venus (copper) can only be to the advantage of our species.

Unraveling of the E-helices and Disruption of 4-Fold Pores Are Associated with Iron Mishandling in a Mutant Ferritin Causing Neurodegeneration

“…The 3-fold pores were basically the same. The main difference in structure between WT-and MT-FTL homopolymers was the lack of E-helices, which have a stabilizing influence on the 24-mer structure through intersubunit interactions among trans-and adjacent pairs of E-helices, as well as through intra-subunit interactions back to their respective subunits (31). The loss of E-helices and the presence of substantial amounts of disorder in the C terminus of the MT-FTL polypeptides lead to a significant disruption of the 4-fold axes pores.…”

Copper-induced ferroportin-1 expression in J774 macrophages is associated with increased iron efflux

“…A role for copper in the release of iron stores is well established (39), and has been thought to primarily involve the need for this metal cofactor to support ceruloplasmin's ferroxidase activity thus facilitating loading of iron onto serum transferrin (8,9). The results of this investigation indicate that, in addition to this function, copper can also regulate the release of iron from macrophages by modifying the expression of the export protein FPN1.…”

Redox Cycling in Iron Uptake, Efflux, and Trafficking

“…As R. J. Williams (91,92) and Robert Crichton (93,94) have emphasized, the common era "metallome" is, in essence, the art of the possible, and for redox-active metal ions like iron and copper, it is the art of what is possible in a tidal pool containing 260 M dissolved O 2 . Starting ϳ2.4 gigayears before the common era (95,96), the redox potential of the geosphere began its slow oxidation from negative (Ϫ400 mV as a lower limit) to positive (ϩ400 mV as an upper limit), and the dominant redoxactive first-row transition metal dissolved in the oceans went from Fe(II) to Cu(II).…”

“…1) Fe(III) is what is available, but it is exchange-inert; for example, its solubility at pH 7.0 is 10 Ϫ18 mol/liter. 2) Fe(II) is soluble and exchanges its ligands readily, but it is a strong pro-oxidant, generating hydroxyl radicals via what is known as the Fenton reaction (93). Yeast, as do we, solve the first problem by ferrireduction, which mobilizes Fe(II) for subsequent metabolism.…”