1. History

At first, the study of biometals was referred to as bioinorganic chemistry. Each branch of bioinorganic chemistry studied separate, particular sub-fields of the subject. However, this led to an isolated view of each particular aspect in a biological system. This view was revised into a holistic approach of biometals in metallomics.^[1]

Metal ions in biology were studied in various specializations. In nutrition, it was to define the essentials for life; in toxicology, to define how the adverse effects of certain metal ions in biological systems and in pharmacology for their therapeutic effects.^[1] In each field, at first, they were studied and separated on a basis of concentration. In low amounts, metal ions in a biological system could perform at their optimal functionality whereas in higher concentrations, metal ions can prove fatal to biological systems. However, the concentration gradients were proved to be arbitrary as low concentrations of non-essential metals (like lithium or helium) in essential metals (like sodium or potassium) can cause an adverse effect in biological systems and vice versa.^[1]

Investigations into biometals and their effects date back to the 19th century and even further back to the 18th century with the identification of iron in blood.^[1] Zinc was identified to be essential in fungal growth of yeast as shown by Jules Raulin in 1869 yet no proof for the need of zinc in human cells was shown until the late 1930s where its presence was demonstrated in carbonic anhydrase and the 1960s where it was identified as a necessary element for humans.^[1] Since then, zinc in human biology has advanced to the point that it is as important as iron. Modern advancements in analytical technology have made it clear the importance of biometals in signalling pathways and the initial thoughts on the chemical basis of life.^[1]

2. Naturally Occurring Biometals

Metal ions are essential to the function of many proteins present in living organisms, such as metalloproteins and enzymes that require metal ions as cofactors.^[2] Processes including oxygen transport and DNA replication are carried out using enzymes such as DNA polymerase, which in humans requires magnesium and zinc to function properly.^[3] Other biomolecules also contain metal ions in their structure, such as iodine in human thyroid hormones.^[4]

Each biometal in your body acts and functions specifically for their respective purpose in your body. The uses of some of them are listed below:

2.1. Calcium

Calcium is the most abundant metal in the eukaryotes and by extension humans. The body is made up of approximate 1.5% calcium and this abundance is reflected in its lack of redox toxicity and its participation in the structure stability of membranes and other biomolecules.^[5] Calcium plays a part in fertilization of an egg, controls several developmental process and may regulate cellular processes like metabolism or learning. Calcium also plays a part in bone structure as the rigidity of vertebrae bone matrices are akin to the nature of the calcium hydroxyapatite.^[5] Calcium usually binds with other proteins and molecules in order to perform other functions in the body. The calcium bound proteins usually play an important role in cell-cell adhesion, hydrolytic processes (such as hydrolytic enzymes like glycosidases and sulfatases) and protein folding and sorting.^[5] These processes play into the larger part of cell structure and metabolism.

2.2. Magnesium

Magnesium is the most abundant free cation in plant cytosol, is the central atom in chlorophyll and offers itself as a bridging ion for the aggregation of ribosomes in plants.^[6] Even small changes in the concentration of magnesium in plant cytosol or chloroplasts can drastically affect the key enzymes present in the chloroplasts. It is most commonly used as a co-factor in eukaryotes and functions as an important functional key in enzymes like RNA Polymerase and ATPase.^[6] In phosphorylating enzymes like ATPase or kinases and phosphates, magnesium acts as a stabilizing ion in polyphosphate compounds due its Lewis acidity.^[5] Magnesium has also been noted as a possible secondary messenger for neural transmissions.^[5] Magnesium acts as an allosteric inhibitor for the enzyme vacuolar pyrophosphatase (V-PP_iase). In vitro, the concentration of free magnesium acts as a strict regulator and stabilizer for the enzyme activity of V-PP_iase.^[6]

2.3. Manganese

Manganese like magnesium plays a crucial role as a co-factor in various enzymes though its concentration is noticeably lower than the other.^[5] Enzymes that use manganese as a co-factor are known as "manganoproteins." These proteins include enzymes, like oxidoreductases, transferases and hydrolases, which are necessary for metabolic functions and antioxidant responses.^[5] Manganese plays a significant role in host defense, blood clotting, reproduction, digestion and various other functions in the body. In particular, when concerning host defense, manganese acts as a preventative measure for oxidative stress by destroying free radicals which are ions that have an unpaired electron in their outer shells.

2.4. Zinc

Zinc is the second most abundant transition metal present in living organisms second only to iron. It is critical for the growth and survival of cells. In humans, zinc is primarily found in various organs and tissues such as the brain, intestines, pancreas and mammary glands.^[7] In prokaryotes, zinc can function as an antimicrobial, zinc oxide nano-particles can function as an antibacterial or antibiotic. Zinc homeostasis is tightly controlled so as to allow it to be high enough to sustain life but not low enough to cause fatalities from its toxicity.^[7] Because of zinc's antibiotic nature, it is often used in many drugs against bacterial infections in humans. Inversely, due to the bacterial nature of mitochondria, zinc antibiotics are also lethal to mitochondria and results in cell death at high concentrations.^[7] Zinc is also used in a number of transcription factors, proteins and enzymes.

2.5. Iodine

Iodine is an essential component of the thyroid hormones thyroxine (T4) and triiodothyronine (T3).^[8] These hormones help to regulate protein synthesis, enzymatic activity and metabolic activity. These hormones are also vital in the development of skeletal and central nervous systems in fetuses and infants.^[8] Iodine levels are normally strictly controlled by thyroid-stimulating hormones (TSHs), or thyrotropins. An increase in TSH causes thyroidal uptake of iodine to increase and stimulates the synthesis and release of T3 and T4.^[8] Deficiency of iodine normally results from inadequate thyroid hormone production secondary to insufficient iodine.^[8] Iodine deficiency affects growth and development detrimentally and by extension, is also the most common cause of preventable intellectual disability in the world.^[8]

3. Biometals in Medicine

Metal ions and metallic compounds are often used in medical treatments and diagnoses.^[9] Compounds containing metal ions can be used as medicine, such as lithium compounds and auranofin.^[10][11] Metal compounds and ions can also produce harmful effects on the body due to the toxicity of several types of metals.^[9] For example, arsenic works as a potent poison due to its effects as an enzyme inhibitor, disrupting ATP production.^[12]

The content is sourced from: https://handwiki.org/wiki/Biology:Biometal