Evolution of metal ions in biological systems

Origins

The Great Oxygenation Event occurred approximately 2.4 Ga (billion years ago) as cyanobacteria induced the presence of dioxygen in earth’s atmosphere. Biological oxidation leading to oxidative stress and cell damage in animals represents one of these types of reactions which are responsible for many animal diseases. Incorporation of metals perhaps combated this. The central chemistry of all these cells has to be reductive in order that the synthesis of the required chemicals, especially biopolymers, is possible. The different anaerobic, autocatalysed, reductive, metabolic pathways seen in the earliest cells we know about developed in separate energised vesicles, protocells, where they were produced cooperatively with certain bases of the nucleic acids.

Redox catalysts

The prebiotic chemistry of life had to be reductive in order to obtain, e.g. CO and HCN from existing CO₂ and N₂ in the atmosphere. Carbon monoxide and HCN were precursor molecules of the essential biomolecules, proteins, lipids, nucleotides and sugars. However, atmospheric oxygen levels increased overtime, and it was then necessary for cells to have control over the reduction and oxidation of such small molecules in order to build and breakdown cells when necessary, without the inevitable oxidation (breaking down) of everything. Transition metal ions, due to their multiple oxidation states, were the only elements capable of controlling the oxidation states of such molecules, and thus were selected for.

Condensation and hydrolysis

O-donors such as HPO2−
4 were abundant in the prebiotic atmosphere. Metal ion binding to such O-donors was required to build the biological polymers, since the bond is generally weak, it can catalyze the required reaction and dissociate after (i.e. Mg²⁺ in DNA synthesis).

Prebiotic (Anaerobic) conditions

Around 4 Ga , the acidic seawater contained high amounts of H₂S and thus created a reducing environment with a potential of around -0.2 V. So any element that had a large negative value with respect to the reduction potential of the environment was available in its free ionic form and can subsequently be incorporated into cells, i.e. Mg²⁺ has a reduction potential of -2.372 V, and was available in its ionic form at that time.

Aerobic conditions

Around 2 Ga, an increase in atmospheric oxygen levels took place, causing an oxidation of H₂S in the surroundings, and an increase in the pH of the sea water. The resulting environment had become more oxidizing and thus allowed the later incorporation of the heavier metals such as copper and zinc.

Irving-Williams series

Another factor affecting the availability of metal ions was their solubilities with H₂S. Hydrogen sulfide was abundant in the early sea giving rise to H₂S in the prebiotic acidic conditions and HS⁻ in the neutral (pH = 7.0) conditions. In the series of metal sulfides, insolubility increases at neutral pH following the Irving-Williams series:

Mn(II) < Fe(II) < Co(II) ≤ Ni(II) < Cu(II) > Zn(II)

So in high amounts of H₂S, which was the prebiotic condition, only Fe was most prominently available in its ionic form due to its low insolubility with sulfides. The increasing oxidation of H₂S into SO2−
4 leads to the later release of Co⁺², Ni⁺², Cu⁺², and Zn⁺² since all of their sulfates are soluble.

Magnesium

Magnesium is the 8th most abundant element on earth. It is the fourth most abundant element in vertebrates and the most abundant divalent cation within cells. The most available form of magnesium (Mg²⁺) for living organisms can be found in the hydrosphere. The concentration of Mg²⁺ in ocean are around 55 mM. Mg²⁺ is readily available to cell during early evolution due to its high solubility in water. Whereas, other transition metals like calcium would precipitate from aqueous solution at much lower concentration than the corresponding Mg²⁺ salts. Since the Mg is readily available in early evolution, Mg can be found in every cell type living organism. Magnesium in Anaerobic prokaryote can be found in MgATP. Magnesium also have many function in prokaryotes such as: glycolytic pathway, all kinases, NTP reaction, signalling, DNA/RNA structures and light capture. In aerobic eukaryotes, magnesium can be found in cytoplasm and chloroplasra. The reaction in this cell compartment are glycolysis, photophosphorylation and carbon assimilation. ATP, the main source of energy in almost all living organism require the presence of Mg²⁺ or Ca²⁺ to function. ATP must bind with metal ion such as magnesium in order to be functioned. Experiment has already proved that magnesium is critical for ATP to function by examining the ATP in cell with limit magnesium supply.The result showed lack of magnesium can cause ATP to decrease. Magnesium in ATP hydrolysis act as co-factor to stabilize the high negative charge transition state. The MgATP can be found in both prokaryotes and eukaryotes cell. However, the most ATP exist in cell are MgATP. Following the Irving–Williams series, magnesium has higher binding constant than the Ca²⁺ . Therefore, the dominate ATP in living organism is MgATP. Great binding constant also given magnesium the advantage as better catalysts over other compete transition metal.

Manganese

Evidence suggests that Manganese was first incorporated into biological systems roughly 3.2 - 2.8 billion years ago, during the Archean Period. Together with calcium, manganese formed the manganese-calcium oxide complex (determined by X-Ray diffraction) which consisted of a manganese cluster, essentially an inorganic cubane (cubical) structure. The incorporation of a manganese center in photosystem II was highly significant, as it allowed for photosynthetic oxygen evolution of plants. The oxygen-evolving complex (OEC) is a critical component of photosystem II contained in the thylakoid membranes of chloroplasts; it is responsible for terminal photooxidation of water during the light reactions. The incorporation of Mn in proteins allowed the complexes the ability to reduce reactive oxygen species in Mn-superoxide dismutatse (MnSOD) and catalase, in electron transfer dependent catalysis (for instance in certain class I ribonucleotide reductases) and in the oxidation of water by Photosystem II (PSII), where the production of thiobarbituric acid-reactive substances is decreased. This is due to manganese's ability to reduce superoxide anion and hydroxyl radicals as well as its chain-breaking capacity.

Iron

Iron (Fe) is the most abundant element in the Earth and the fourth most abundant element in the crust. Iron encompasses roughly 5 percent by mass of today's crust. Due to the abundance of iron and its role in biological systems, the transition and mineralogical stages of iron have played a key role in Earth surface systems. Iron played larger role in the geological past in marine geochemistry, as evidenced by the deposits of Precambrian iron-rich sediments. The redox transformation of Fe(II) to Fe(III), or vice versa, plays a big role in a number of biological and element cycling processes. The reduction of Fe(III) is seen to oxidize sulfur (from H₂S to SO₄^-2), which is a central process in marine sediments. Many of the first metalloproteins consisted of iron-sulphur complexes formed during photosynthesis. Iron is the main redox metal in biological systems. In proteins, it is found in a variety of sites and cofactors, including, for instance, haem groups, Fe–O–Fe sites, and iron–sulfur clusters. The prevalence of iron is apparently due to the large availability of Fe(II) in the initial evolution of living organisms, before the rise photosynthesis and of atmospheric oxygen levels which resulted in the precipitation of iron in the environment as Fe(OH)₃. Iron also has flexible redox properties because such properties are sensitive to ligand coordination, including geometry. Iron can be also used in enzymes due to its Lewis acid properties an example of this is that of nitrile hydratase. Iron is frequently found in mononuclear sites in the reduced Fe(II) form, and functions in dioxygen activation, this function is used as a major mechanism adopted by living organisms to avoid the kinetic barrier hindering the transformation of organic compounds by O₂. Iron can be taken up selectively as ferredoxins, Fe-O-Fe (hemerythrin and ribonucleotide reductase), Fe (many oxidases), apart from iron porphyrin. Variation in the related proteins with any one of these chemical forms of iron has produced a wide range of enzymes. It is important to understand that all these arrangements are modified to function both in the sense of reactivity and its positioning of the protein in the cell. In many cases the iron can have many redox and spin states and, it can be held in many stereochemistries.

Nickel and Cobalt

Around 4-3 Ga, anaerobic prokaryotes began developing metal and organic cofactors for light absorption. They ultimately ended up making chlorophyll from Mg(II), as is found in cyanobacteria and plants, leading to modern photosynthesis. However, chlorophyll synthesis requires numerous amounts of steps. The process starts with uroporphyrin, a primitive precursor to the porphyrin ring which may be biotic or abiotic in origin, which is then modified in cells differently to make Mg, Fe, Ni, and Co complexes. The center of these rings are not selective, thus allowing the variety of metal ions to be incorporated. Mg porphyrin gave rise to chlorophyl, Fe porphyrin gave rise to heme proteins, Ni porphyrin gave rise to factor F-430, and Co porphyrin gave rise to Coenzyme B12.

Copper

Before the Great Oxygenation Event, copper was not much available for the living organism. Most early copper was Cu⁺ and Cu. This oxidation state copper were not very soluble in water. One billion years ago, after the great oxidation event the oxygen pressure was higher enough to oxides Cu⁺ to Cu²⁺, Cu²⁺ is more soluble in water. Cu becomes more soluble when reacting with oxygen and passing from Cu⁺ to Cu²⁺. As the result, the immobilize copper became mobilized and much more available for living organism. The most copper contain protein and enzyme can be found in eukaryotes. Only handful of prokaryotes such as aerobic bacteria and cyanobacteria can be found contain copper enzyme or protein. Copper can be found in both prokaryotes and eukaryotes superoxide dismutase enzyme. There were three type of superoxide dismutase. The three distinct SOD contain Mn, Fe and Cu respectively. The Mn-SOD and Fe-SOD are found in most prokaryotes and mitochondria of the eukaryotic cell. Cu-SOD can be found in the cytoplasmic fraction of the eukaryotic cells. The three element: copper, iron and manganese can all catalytic superoxide to ordinary molecular oxygen or hydrogen peroxide. However, comparing the efficiency of the catalysis, Cu-SOD is more efficient than Fe-SOD and Mn-SOD. The most prokaryote only utilize Fe-SOD or Mn-SOD is due to the lack of copper in the environment. Some organism also did not develop Cu-SOD due to lack of gene pool for the Cu-SOD adoption.

Zinc

Zinc was incorporated into living cells in two waves throughout time. Four to three Ga, anaerobic prokaryotes rose, and the atmosphere was full of H₂S and highly reductive. So, zinc was mainly in the ZnS form (insoluble form), but since the sea water at the time was slightly acidic, some Zn(II) was available in its ionic form and thus some managed to become part of early anaerobic prokaryotes’ external proteases, external nucleases, internal synthetases and dehydrogenases. During the second wave, GOE has occurred, and more Zn(II) ions were available in the sea water. This allowed its incorporation in the single-cell eukaryotes (as they arose at this time). It is believed that the later addition of ions such as zinc and copper allowed them to displace Fe and Mn from the enzyme, superoxide dismutase. Fe and Mn complexes dissociate readily (Irving-Williams series) while Zn and Cu do not. This is why eukaryotic superoxide dismutase contains Cu or Zn and prokaryotic counterpart contains Fe or Mn. Zn (II) doesn’t pose an oxidation threat to the cytoplasm. This allowed it to become a major cytoplasmic element in the eukaryotes. It became associated with a new group of transcription proteins, Zinc fingers. This could only have occurred due to the long life of eukaryotes, which gave time for zinc to exchange and hence become an internal messenger coordinating the action of other transcription factors during growth.

Molybdenum

Molybdenum (Mo) is the most abundant transition element in solution in the sea (mostly as dianionic molybdate ion) and in living organisms, its abundance in the Earth’s crust is quite low. Therefore, the use of Mo by living organisms seems surprising at first glance. Archaea, bacteria, fungi, plants, and animals, including humans, require molybdenum. It is also found in over 50 different enzymes. Its hydrolysis to water-soluble oxo-anionic species makes Mo readily accessible. Mo is found in the active sites of metalloenzymes that perform key transformations in the metabolism of carbon, nitrogen, arsenic, selenium, sulfur, and chlorine compounds. The mononuclear Mo enzymes are widely distributed in the biosphere; they catalyze many significant reactions in the metabolism of nitrogen and sulfur-containing compounds as well as various carbonyl compounds (e.g., aldehydes, CO, and CO₂). Nitrate reductases enzymes are important for the nitrogen cycle. They belong to a class of enzymes with a mononuclear Mo center and they catalyze the metabolism reaction of C, N, S, etc., in bacteria, plants, animals, and humans. Due to the oxidation of sulfides, The first considerable development was that of aerobic bacteria which could now utilize Mo. As oxygen began to accumulate in the atmosphere and oceans, the reaction of MoS₂ to MoO₄ also increased. This reaction made the highly soluble molybdate ion available for incorporation into critical metalloenzymes, and may have thus allowed life to thrive. It allowed organisms to occupy new ecological niches. Mo plays an important role in the reduction of dinitrogen to ammonia, which occurs in one type of nitrogenases. These enzymes are used by bacteria that usually live in a symbiotic relationship with plants; their role is nitrogen fixation, which is vital for sustaining life on earth. Mo enzymes also play important roles in sulfur metabolism of organisms ranging from bacteria to humans.

Tungsten

Tungsten is one of the oldest metal ions to be incorporated in biological systems, preceding The Great Oxygenation Event. Before the abundance of oxygen in Earth's atmosphere, oceans teemed with sulfur and tungsten, while molybdenum, a metal that is highly similar chemically, was inaccessible in solid form. The abundance of tungsten and lack of free molybdenum likely explains why early marine organisms incorporated the former instead of the latter. However, as cyanobacteria began to fill the atmosphere with oxygen, molybdenum became available (molybdenum becomes soluble when exposed to oxygen) and molybdenum began to replace tungsten in the majority of metabolic processes, which is seen today, as tungsten is only present in the biological complexes of prokaryotes (methanogens, gram-positive bacteria, gram-negative aerobes and anaerobes), and is only obligated in hyperthermophilic archaea such as P. furiosus. Tungesten's extremely high melting point (3,422^oC), partially explains its necessity in these archaea, found in extremely hot areas.

Although research into the specific enzyme complexes in which tungsten is incorporated is relatively recent (1970s), natural tungstoenzymes are abundantly found in a large number of prokaryotic microorganisms. These include formate dehydrogenase, formyl methanufuran dehydrogenase, acetylene hydratase, and a class of phylogenetically related oxidoreductases that catalyze the reversible oxidation of aldehydes. The first crystal structure of a tungsten- or pterin-containing enzyme, that of aldehyde ferredoxin oxidoreductase from P. furiosus, has revealed a catalytic site with one W atom coordinated to two pterin molecules which are themselves bridged by a magnesium ion.