Humans Require Minute Quantities of Several Inorganic Elements
The organic elements oxygen, carbon, hydrogen, nitrogen, sulfur, and phosphorous typically account for slightly more than 97% of the mass of the human body. Calcium, the majority of which is contained in bones, teeth, and cartilage, contributes a further ≈ 2%. The remaining 0.4 to 0.5% is accounted for by numerous inorganic elements (Table 1). Many of these are essential for health, albeit in minute quantities, and thus are commonly classified asmicronutrients. Examples of physiologically essential micronutrients include iodine, which is required for the synthesis of tri- and tetraiodothyronine; selenium, which is required for the synthesis of the amino acid selenocysteine; and vitamins. The focus of the current chapter will be on the physiologic roles of the nutritionally essential transition metals iron (Fe), manganese (Mn), zinc (Zn), cobalt (Co), copper (Cu), nickel (Ni), molybdenum (Mo), vanadium (V), and chromium (Cr).

Table1. Quantities of Selected Elements in the Human Body
Transition Metals Are Multivalent
One common characteristic of metals is their propensity to undergo oxidation, a process in which they donate one or more electrons from their outer or valence shell to an electronegative acceptor species, for example, molecular oxygen. Oxidation of an alkali or alkaline earth metal (Figure 1) results in a single ionized species, for example, Na+, K+, Li+, Mg2+, or Ca2+. By contrast, the oxidation of transition metals can yield multiple valence states (Table 2). This capability enables transition metals to undergo dynamic transitions between valence states through the addition or donation of electrons, and therefore to function as an electron carrier during oxidation–reduction (redox) reactions. The ability of transition metals to act as acids further expands their biologic roles.

Fig1. Periodic table of the elements. Transition metals occupy columns 3 to 11, also labeled 1B to 8B.

Table2. Valence States of Essential Transition Metals
Transition Metal Ions Are Potent Lewis Acids
In addition to serving as electron carriers, the functional capabilities of the nutritionally essential transition metals are enhanced by their ability to act as Lewis acids. Protic (Bronsted Lowry) acids can donate a proton (H+) to an acceptor with a lone pair of electrons, for example, a primary amine or a molecule of water. Lewis acids, by contrast, are aprotic. Like H+ ions, Lewis acids possess empty valence orbitals capable of noncovalently associating with or “accepting” a lone pair of electrons from a second, “donor” molecule. When the ferrous (Fe2+) iron in myoglobin and hemoglobin bind oxygen or other diatomic gases such carbon monoxide, they are acting as Lewis acids. Divalent Zn2+ or Mn2+ can serve as Lewis acids during catalysis by hydrolytic enzymes, specifically by enhancing the nucleophilicity of active-site water molecules.