Answer:
Dr. Eiichiro Ochiai, who is studying bioinorganic chemistry, kindly answered the question above. He briefly discusses in general terms the requirement of metallic elements by organisms and then illustrates the biological use of elements by one of the most widely used metallic element, iron (Fe). So the following is titled as “A Story of Iron” (© Eiichiro Ochiai). 
 
 
We living organisms are made of, chemically speaking, mostly organic compounds such as proteins, nucleic acids, carbohydrates, vitamins and so on. Organic compounds are made of mainly carbon (C), hydrogen (H), oxygen (O) and nitrogen (N). Some organic compounds may also contain sulfur (S) or phosphorus (P). That’s it; no other. Can we live well with only organic compounds? Most people know the answer is “NO”. Our bones and teeth are made of calcium (Ca) compounds, which are “inorganic (not-organic)” ones. Blood contains iron (Fe), an inorganic element. Everybody knows that we need salt (sodium chloride, NaCl), though (s)he may not know why. In fact, about 30 elements are known to be essential for the proper functioning of living organisms. As most of you know, there are only about 100 elements or so in this universe, and about one third of all the elements are necessary for the living organisms. Important among them are (other than those already mentioned): magnesium (Mg), silicon (Si), potassium (K), manganese (Mn), cobalt (Co), copper (Cu), zinc (Zn), molybdenum (Mo), iodine (I), selenium (Se), nickel (Ni) and boron (B). A new research field has now emerged, that studies what roles these different elements and their compounds play in the biological systems; it is called “bioinorganic chemistry”. It is way too large a topic to deal with in this kind of forum; hence I have chosen a particular element, iron and illustrate the discipline called bioinorganic chemistry. The first section “Formation of Element Iron” is not a proper topic of bioinorganic chemistry, but added here to tell you an important fact about Iron.
 
I am sure that everybody is familiar with the metal iron. Cars and machines are made mainly of iron. Iron is one of the most abundantly available and most interesting elements in the universe, as well as one of the crucial elements for living organisms. Here is a story of iron. 
 
Formation of Element Iron 
At the very beginning, there was a fireball of an enormously high temperature (that is, of huge energy) you cannot imagine. It exploded at the time zero of the beginning of this universe. It is known as “BIG BANG”. As the exploding sphere expanded, the temperature started to drop. There was yet no material as we know of, and it was only the energy; there was nothing, no sun, no star, no galaxy, let alone elephant or human. As the temperature dropped further, the energy started to turn to material. It was a real materialization; material emerges from nothing (or rather energy). This process can be made sense referring to the famous equation by Einstein: E=mc². “E” represents energy, and “m” is mass and represents the material. This equation implies that mass and energy are equivalent; so that energy can turn into material or material can turn into energy. The first material thus emerged is the simplest matter: proton (the nucleus of hydrogen atom whose chemical symbol is H); actually the first material that emerged are fundamental particles called quarks. A certain combination of three quarks makes up a proton. Likewise, a similar but different combination of quarks gave rise to another nucleon called neutron. We are talking about only those fundamental particles that are relevant to this discourse. One proton and one neutron combines to form another nucleus of hydrogen known as heavy hydrogen or deuterium (chemical symbol=D). A proton carries a unit of electric charge, whereas a neutron is electrically neutral. Eventually another kind of fundamental particle, electron, formed. An electron carries the same unit of electric charge as that of a proton, but of the opposite sign. The sign of the electric charge of a proton is defined as “positive”, so that that of electron is “negative”. As the temperature of the universe drops further, a proton combines with an electron, forming an atom of hydrogen. Deuterium was formed likewise. Hydrogen and deuterium atoms come together (by gravity) and forms a star like sun, and the cloud of particle becomes so dense that the temperature goes up. When the temperature becomes high enough, the nuclei of hydrogen/deuterium start to combine themselves. One of the major events in that situation is formation of helium (He) from hydrogen/deuterium. Helium has a nucleus consisting of two protons and two neutrons. This is the major event happening in our Sun. The total mass of two protons and two neutrons become smaller as they fuse together (called “nuclear fusion”) to form helium. The mass lost in the process turns back to energy through the same relationship E=mc². We are all relying on this energy for sustenance of our lives. 
 
The above is an outline of the earlier part of processes of formation of elements in the universe. We have to discuss more in order to fully understand the formation of elements in the universe, but that is not our intention here. Suffice to say, iron atom was formed through further such nuclear reactions in stars. 
 
An iron atom has a nucleus containing 26 protons and 30 neutrons. But this is not all; there are a few other iron atoms that have the same number of protons but different number of neutrons. These atoms are called “isotopes” of element iron. But the isotope that has 26 protons and 30 neutrons (technically expressed ₂₆Fe⁵⁶; 56= the total number of protons and neutrons) is the major isotopes (i.e., the most abundant one). (By the way you will realize from this description that hydrogen H and deuterium D are isotopes.) We will discuss this isotope (₂₆Fe⁵⁶) of iron mostly from now on. 
 
The nuclear binding energy per nucleon (NBEPN) is defined as the energy released in forming a nucleus from separate protons and neutrons divided by the total number of protons and neutrons; this energy NBEPN hence represents how stable the nucleus is. NBEPN has been determined for all nuclei present in the universe. It turned out that isotope ₂₆Fe⁵⁶ is the most stable in this sense of all the atoms present in the universe. Other stable atoms in this sense include helium (₂He⁴), carbon (₆C¹²), oxygen (₈O¹⁶), silicon (₁₄Si²⁸). These are the elements most abundantly found in the universe beside hydrogen. It is interesting to note that these elements constitute the major material in the universe: H/He in the Sun and similar stars, C/O/H in the living organisms on the earth, and Si/Fe in the rocks on the earth. 90% or more of all the meteorites falling on the earth is made of iron and nickel. Nickel consists mainly of ₂₈Ni⁵⁸ and ₂₈Ni⁶⁰ and is quite abundant in the universe (not necessarily so on the earth), because its NBEPN is quite high (not so high as Fe). You will note that there is Co between Fe and Ni in the periodic table. Element Co is much less abundant in the universe compared to its neighbors Fe and Ni. In fact elements with an even number of protons and neutrons are much more abundant than the neighboring elements with an odd number of protons (and in general of neutrons as well).
 
The point to be made here is that iron is one of the most abundant elements in the universe and on the earth as well.
 
Necessity for Inorganic Elements
We will briefly consider the issue: why inorganic compounds are necessary for the proper functions of biological systems?; why not organic compounds alone suffice?. 
  
In terms of weight, 70 % or so of our body is actually water, and the remaining 30 % or so are solid substances. This percent varies from a species to another and also depends on conditions. It is true that the major part of the solid substances is made up of organic compounds such as those mentioned earlier. Proteins provide us with muscle and other important biocompounds called “enzymes”, nucleic acid such as DNA and RNA provide the genetic material, and carbohydrates are the energy source. These compounds provide living organisms with the vital services. So are they sufficient?
  
The compounds play their roles through “chemical” reactions. For examples, carbohydrates have to be metabolized in order for them to provide energy for us. Metabolism consists of a fairly large number of chemical reaction steps. Proteins will be first partially digested in stomach; proteins are chopped down to smaller sizes. This is technically a “hydrolysis” reaction. A ribonucleotide has to be converted into the corresponding deoxyribonucleotide. Four different kinds of deoxyribonucleotides combine to form a sort of linear chain; the resulting chain is called “DNA” (deoxyribonucleid acid), the gene. Virtually all these chemical conversions, i.e., chemical reactions cannot take place readily. They require something that would speed up chemical reactions; this something is called “catalyst”. All the biological chemical reactions require special kinds of catalysts, which are called “enzymes”. Most of enzymes are made of proteins. Some ribonucleic acids (RNA) have in recent years been found to exhibit catalytic effects; such a catalytic RNA is called “ribozyme”. 
 
Both enzymes and ribozymes are organic compounds. Indeed many of them made of only carbon, hydrogen, nitrogen, oxygen, sulfur and phosphorus. They can carry out the catalytic effects as such. However, a large number of enzymes/ribozymes, perhaps more than 30% of all, need more than organic entities. They require metallic elements added for the full catalytic activities. The reason is that what the elements C, H, O, N, S and P can do (in chemical sense) is quite limited. 
 
There are essentially two different types of chemical (as well as biochemical) reactions; one is “acid-base” and the other “oxidation-reduction”. A catalyst should be able to assist in one of these reactions; that is, the catalyst itself need to be either “acid (or base)” or “oxidizing agent (or reducing agent)”. The organic compounds have only a limited capability either as acid (or base) or oxidant (or reductant). 
 
“Oxidation-reduction” reactions involve an exchange of electron(s). For example, iron metal will rust in the air; it is an oxidation reaction. What happens is as follows. Iron atom in the metal has 26 electrons and hence the electric charge of the atom is zero; technically it can be expressed as Fe(0), and is said to be in the “0” oxidation state. Oxygen in the air is an oxidizing agent, and removes electrons from the metallic iron Fe(0). When the iron atom has lost, say two electrons (now it has only 24 electrons), it would become +2 in the electric charge; it is expressed as Fe(II) (or Fe²⁺). (An electrically charged entity is called “ion” in general). The oxidation state of this atom is now +2 (or II). It can further lose easily another electron, and turns to Fe(III). Meanwhile the oxygen (O₂) gains electron(s) from the iron entity and turns into 2O^2-. The oxidation state of this entity is –2. The rust consists mainly of a compound Fe₂O₃ which is the product of this oxidation reaction. As implied here, Fe(II) can be readily converted to Fe(III), and this is the major reason for the usefulness of iron in the biochemical reactions. That is, iron can change its oxidation states easily so that it can give or take electron(s) very readily. A large number of biochemical reactions, particularly those involved in energy production, involve oxidation-reduction, and the iron entity is one of the best catalysts to assist such reactions. Other inorganic elements such as manganese, copper and molybdenum are also good in assisting biochemical oxidation-reduction reactions. 
 
Metallic ions such as Zn(II) (Zn²⁺) and Mg(II) provide enzymes with a good acid capability. Hence a number of enzymes for “acid-base” type of reaction use Zn(II) or Mg(II) as their active center (where the reaction takes place).
 
Sodium ion (Na(I)) and potassium ion (K(I)) create an electric potential across the cell membrane, because an unequal distribution of them inside and out give rise to a different amount of electric charge inside and out. This is exactly what the electric potential is. The electric potential across the membrane of neuronal cell is the basis of the nerve signal. Calcium (Ca(II)) ion plays a large number of roles in cell physiology. For example, when a neuronal signal arrives at a muscle, it induces a discharge of calcium into the cell, and that triggers the muscle contraction. Bleeding from your injury will stop soon, because blood clotting. This process, blood clotting, would not happen without Ca(II). These are just two examples in which Ca(II) plays vital roles. It is not an exaggeration that cells with its associated functions would not exist as such without calcium.
  
Organic compounds may never be very strong mechanically. Inorganic compounds provide some mechanical strength to living organisms. Egg shell is calcium carbonate (CaCO₃), bone and dentine are made of mainly calcium phosphate (Ca₃(PO₄)₂). Some organisms (plants and sea creatures) use silica (SiO₂) for the same purpose.
These are the major roles played by inorganic compounds in the biological systems, and, I hope, you see that the organic compounds cannot provide these functions.
 
Acquisition of Iron by Biological Systems
It was indicated earlier that metals other than iron can play catalytic roles in oxidation-reduction. Then why did the organisms pick and use iron instead of, say, copper? There are two reasons. The reasons are the same as those by which you choose a building material for example. You would choose a material based on two criteria, wouldn’t you?: (1) Suitability (is the material suitable for the purpose?) and (2) Economy (readily available, including price?). Issue (1) is rather difficult, unless you know a lot of chemistry. But suffice to say that most of the functions that iron carries out cannot be provided by copper. 
 
Issue (2) is easy to provide an answer for. As we mentioned before (see the section on “formation of element iron”), iron is one of the most abundant elements in the universe and on the earth as well. That is why. Well it is true but is it readily available? It is interesting to note that today on this earth the living organisms tend to be deficient of iron. We often have to take iron-supplement. Many organisms have to try hard to get enough iron from the environment. This implies that iron is not readily available. Again this is also true. So what’s going on? 
 
The truth is that the availability of iron (not the quantity) has changed dramatically over the long history of the earth. This has a lot to do with the oxygen content in the atmosphere. This requires a long discourse, but again it would be sufficient to note that the oxygen in the atmosphere was almost nil up until about 2.2 billion years ago. The free oxygen in the air has been produced by water–decomposing photosynthesis, first by cyanobacteria, then other microorganisms such as phytoplanktons, and eventually terrestrial green plants. It is believed that photosynthetic cyanobacteria emerged sometime around 3 billions years ago. When the atmosphere lacked oxygen, the sea water contained a lot of iron in the form of Fe(II), because it is soluble in water. However, when oxygen became available through photosynthesis, Fe(II) got oxidized to Fe(III) (recall the formation of rust). Fe(III) is not soluble in water, coming out of water as Fe(OH)₃. By the way, Fe(OH)₃ turns to Fe₂O₃ ores, and this is the major iron ore found on the earth today. More oxygen was produced by photosynthetic microorganisms and that produced more iron oxide ores, until the iron in the ocean was almost exhausted. Then the oxygen in the air started rose rapidly. When iron precipitates as solid hydroxide or others, iron become unavailable for the organisms, because organisms can pick up iron only when it is dissolved in water. That is essentially what happened over the long history of the earth. On the ancient earth the seawater contained a lot of iron so that the then-evolving organisms gladly used the very useful iron that was also readily available. Thereafter, all the organisms evolved later had to use mechanisms developed earlier so that virtually all the organisms existent on the present earth use iron, but now the oxygen content of the atmosphere is so high that the iron has become difficult to obtain, because most of it exists now as solid Fe(OH)₃ or Fe₂O₃. 
 
So, you can see why human body for example has an elaborate array of mechanisms to squeeze out the scarce iron from the food and keep it recycled in the body. Our body uses energy to absorb much of iron, and has a storage of iron when iron is present in excess. There is a lot of interesting chemistry in this regard, but we cannot elaborate it here.
  
An interesting sequel to this issue is that copper was not available to organisms in the ancient seawater when the atmospheric oxygen was very low. Therefore, only organisms that emerged relatively recent (perhaps after about 1,8 billions years ago) could use copper; indeed copper is found mostly in the more evolved organisms, eukaryotes, but not in lower organisms (of course there are a few exceptions). This difference between iron and copper is due to a difference in a simple chemical character; iron is very easily oxidized and hence iron exists mostly in the form of iron oxide ores. Indeed the majority of iron ores found on the earth is various forms of iron oxides, as stated earlier. On the other hand copper exist even today in the form of metal (i.e., reduced form), though today there are a number of oxidized form of copper ores. In other words, copper is more difficult to oxidize; you might have noticed that a copper pipe lasts shiny very long. Or we could say that copper metal is more stable than oxidized copper compounds. So for the copper to become available to organisms, i.e., soluble in water (in the form of Cu(II)), the atmospheric oxygen level had to become significant. 

Biological Functions of Iron
Biological functions of iron will be surveyed briefly. An average adult human body contains 4 to 5 grams of iron. It doesn’t sound a lot, but in fact it is a lot. Zinc is the next abundant micronutrient; 2-3 grams of it is present in human body. Except for calcium, magnesium, sodium, and potassium, the quantities of other essential inorganic elements in the body are minute; these are called “micronutrients”. 
 
A large part of iron (60-70%) in human body is contained in red blood cell, though every single cell in the body contains iron. Iron in the red blood cells is actually contained in a protein called hemoglobin. It carries oxygen throughout our body. Hemoglobin consists of a protein (called globin) and a small group called “heme” which is where iron is located. Hemoglobin is typical of heme proteins. There are a large number of heme-containing proteins in our body. Examples include myoglobin, cytochrome a, cytochrome b, cytochrome c, cytochrome c oxidase, catalase and cytochrome P450. They all function by changing the iron’s oxidation states, mainly II and III. The iron does give up or take up an electron when it switches between II and III. Cytochromes a, b, c and others are mostly involved in relaying electron(s) from a component to another in respiratory systems where food is eventually burned to carbon dioxide and water and energy is produce, and other systems. 
 
Let’s look at the situation of hemoglobin. When it is in Fe(II), it can bind O₂ (say in lung). When hemoglobin with oxygen bound then is carried to a place where O₂ is scarce, say, active muscle cells, it would give up O₂. In terms of chemical reaction, binding of O₂ to hemoglobin can be written as:
  

O₂ + Fe(II) (hemoglobin) ↔ O₂--Fe(III) (hemoglobin)

 
This equation implies that the reaction can go both ways, forward and backward, and such a reaction is called “reversible”. By the way, the O₂ released from hemoglobin is then accepted by another heme protein myoglobin in the muscle cell.
 
The iron in catalase and cytochrome P450 seems to take other higher oxidation states when they are operating, but it is a long story to tell and is still controversial in today’s research. Catalase is an enzyme found in your blood for instance. You might have had this experience. When you get your finger injured with blood streaming out, you would have a disinfectant solution applied to it. The solution contains a chemical called “hydrogen peroxide” which is a strong oxidant and kills the germs. But often you might have noticed bubble coming up from your blood. It is what catalase is doing. Catalase decomposes hydrogen peroxide and makes oxygen (O₂) gas. That is the bubble. Cytochrome P450 containing enzymes (and there are many) are very important in metabolizing a large variety of substances such as steroids, medicines and other extraneous substances. It functions by incorporating the oxygen atom of O₂ into a chemical (technically termed as “substrate); this is an example of oxygenation reaction (see below).
 
There is another class of iron compounds that are involved in relaying electrons. They are collectively called “iron-sulfur” proteins. The major ones are [Fe₂S₂] and [Fe₄S₄]. Some of the proteins containing these units are called “ferredoxin”s. The [Fe₂S₂] unit has a structure in which two Fe’s are doubly bridged by S^2- ions. Each of Fe’s are also bound to the protein through two amino acid (called cysteine) residues. This ferredoxin is an important electron carrier in the photosynthesis of green leaves. The [Fe₄S₄] unit takes a cube shape (approximately), in which 4 Fe’s and 4S^2-‘s occupy alternate apical positions. Both of these units [Fe₂S₂] and [Fe₄S₄] move electrons around by changing the oxidation states of the Fe between Fe(II) and Fe(III). It turned out that iron-sulfur proteins play roles other than electron-transfer. For example, an enzyme called aconitase contains [Fe₄S₄] unit but its function is not to transfer electrons but rather one of the Fe’s acts as an acid. Yet another function of [Fe₄S₄] is to monitor the level of oxygen (O₂) in certain cells. 
 
One important iron-sulfur related enzyme is “nitrogenase”. Nitrogenase is the enzyme which converts nitrogen (N₂) in the air to ammonia (NH₃). Ammonia is then utilized by plants. This process is called nitrogen fixation conducted by microorganisms, and a critical component in the entire ecological system on the earth. Anyway, this enzyme contains a rather complicated unit consisting of an exotic element, molybdenum (Mo) associated with a special type of iron-sulfur unit. 
 
There are a whole variety of iron-containing enzymes that do not have specific units such as heme or iron-sulfur. A few examples will suffice. Enzymes that contain a single Fe(II) or Fe(III) react with O₂ and a substrate and introduce either one of or both of O atoms of O₂ into the substrate. These enzymes are collectively called oxygenases, and involved in metabolizing a diverse range of organic compounds. Examples are: catechol dioxygenase, pterin-dependent phenylalanine hydroxylase and a-ketoglutarate dependent proline monooxygenase. Methane monooxygenase is an enzyme to convert methane to methanol, and contains two Fe’s locked together. 
 
We can go on like this quite a bit more, but let us finish this discourse by giving you another example of interesting use of iron compound by organisms. How do a little creature navigate their movement? Do they have a navigator? Yes, it turned out that some of them do. A bacterium called Magnetospirillum magneticum uses a string of magnetic substance, magnetite Fe₃O₄ (a kind of iron oxide, a tiny magnet), as a sort of needle of compass. As you know, the needle of compass is magnetized so that the needle aligns itself parallel to the magnetic field of the earth, usually north to south. 
 
References

• Ochiai, E., “Life and Metals” (Kyoritu-Shuppan, Tokyo, 1991, in Japanese)

• Ochiai, E., “General Principles of Biochemistry of the Elements” (Plenum Press, New York, 1987)

• Ochiai, E., Biogeochemical Cycling of Macronutrient, Encyclopedia of Life Support Systems, 1.1.10.2. (UNESCO, 2001)

• Ochiai, E., Biogeochemical Cycling of Micronutrients and others”, Encyclopedia of Life Support Systems, 1.1.10.3. (UNESCO, 2001)

  
Acknowledgement
We would like to thank Dr. Eiichiro Ochiai for his kind answer.