Biometal (biology)

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Element percentages in the human body. 201 Elements of the Human Body-01.jpg
Element percentages in the human body.

Biometals are metals normally present, in small but important and measurable amounts, in biology, biochemistry, and medicine. The metals copper, zinc, iron, and manganese are examples of metals that are essential for the normal functioning of most plants and the bodies of most animals, such as the human body. A few (calcium, potassium, sodium) are present in relatively larger amounts, whereas most others are trace metals, present in smaller but important amounts (the image shows the percentages for humans). Approximately 2/3 of the existing periodic table is composed of metals with varying properties, [1] accounting for the diverse ways in which metals (usually in ionic form) have been utilized in nature and medicine.

Contents

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. [2]

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. [2] 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. [2]

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. [2] 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. [2] Since then, understanding of zinc in human biology has advanced to the point that it is considered 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. [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. [3] 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. [4] Other biomolecules also contain metal ions in their structure, such as iodine in human thyroid hormones. [5]

The uses of some of them are listed below. The list is not exhaustive, because it covers only the principal class members; others that are trace metals of especially low bioconcentration are not explored herein. Some elements that are nonmetals or metalloids (such as selenium) are beyond the scope of this article.

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. [6] 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. [6] 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. [6] These processes play into the larger part of cell structure and metabolism.

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. [7] 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. [7] In phosphorylating enzymes like ATPase or kinases and phosphates, magnesium acts as a stabilizing ion in polyphosphate compounds due its Lewis acidity. [6] Magnesium has also been noted as a possible secondary messenger for neural transmissions. [6] Magnesium acts as an allosteric inhibitor for the enzyme vacuolar pyrophosphatase (V-PPiase). In vitro, the concentration of free magnesium acts as a strict regulator and stabilizer for the enzyme activity of V-PPiase. [7]

Manganese

Manganese like magnesium plays a crucial role as a co-factor in various enzymes though its concentration is noticeably lower than the other. [6] 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. [6] 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.

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. [8] In prokaryotes, zinc can function as an antimicrobial, zinc oxide nano-particles can function as an antibacterial or antibiotic. Zinc homeostasis is highly controlled to allow for its benefits without risk of death via its high toxicity. [8] 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. [8] Zinc is also used in a number of transcription factors, proteins and enzymes.

Sodium

Sodium is a metal where humans have discovered a great deal of its total roles in the body as well as being one of the only two alkali metals that play a major role in the bodily functions. It plays an important role in maintenance of the cell membrane potential and the electrochemical gradient in the body via the sodium-potassium pump and sodium-glucose transport proteins. Sodium also serves a purpose in the nervous system and cell communication as they flood into axons during an action potential to preserve the strength of the signal. [9] It has also been shown that sodium affects immune response both in efficiency and speed. Macrophages have increased proliferation rates at high-salt concentrations and the body uses high-sodium concentrations in isolated regions to generate an heightened immune response which fades after the infection has been dealt with. [10]

Potassium

In plants, potassium plays a key role in maintaining plant health. High concentrations of potassium in plants play a key role in synthesis of essential proteins in plants as well as development of plant organelles like cell walls to prevent damage from viruses and insects. [11] It also lowers the concentration of low molecular weight molecules like sugars and amino acids and increases the concentration of high weight molecular weight molecules like protein which also prevent the development and propagation of viruses. [11] Potassium absorption has a positive correlation with aquaporins and the uptake of water in plant cells via cell membrane proteins. [11] Because of this correlation, it has been noted that potassium also plays a key part in stomatal movement and regulation as high concentrations of potassium are moved into the plant stomata to keep them open and promote photosynthesis. [11] In animals, potassium also plays a key part along with sodium in maintaining resting cell membrane potential and in cell-cell communication via repolarization of axon pathways after an action potential between neurons. [9] Potassium may also play a key part in maintaining blood pressure in animals as shown in a study where increased severity of periodontal disease and hypertension were inversely correlated to urinary potassium excretion (a telltale sign of low potassium intake). [12]

Iron

Iron is also the most abundant transition metal in the human body and it is used in various processes like oxygen transport and ATP production. It plays a key role in the function of enzymes like cytochrome a, b and c as well as iron-sulfur complexes which play an important role in ATP production. [13] It is present in every type of cell in the brain as the brain itself has a very high energy requirement and by extension a very high iron requirement. [13] In animals, iron plays a very important role in transporting oxygen from the lungs to tissues and CO2 from tissues to the lungs. It does this via two important transport proteins called hemoglobin and myoglobin. [14] Hemoglobin in the blood transports oxygen from the lungs to myoglobin in tissues. Both proteins are tetramer complexes with iron protein complexes called hemes built into each subunit of the tetramer. The oxygen binds to the iron in the heme via affinity-based binding or liganding and dissociates from the protein once it has reached its destination. [14] Iron can also be a potential carcinogen in three ways; first being the production of hydroxyl radicals. Ferric ions can be reduced via superoxide and the product can be reoxidized via peroxide to form hydroxyl radicals. Hydroxyl radicals and other reactive oxygen species when generated near DNA can cause point mutations, cross-linkage and breaks. [15] The second being the bolstering of the growth of neoplastic cells by suppressing host defenses. Excessive iron inhibits the activity of CD4 lymphocytes and suppresses the tumoricidal activity of macrophages. [15] The third way it can act as a carcinogen is by functioning as an essential nutrient for unrestricted proliferation of tumor cells. [15]

Lithium

Lithium is present in biological systems in trace amounts; its functions are uncertain. Lithium salts have proven to be useful as a mood stabilizer and antidepressant in the treatment of mental illness such as bipolar disorder.

Biometals in medicine

Metal ions and metallic compounds are often used in medical treatments and diagnoses. [16] Compounds containing metal ions can be used as medicine, such as lithium compounds and auranofin. [17] [18] Metal compounds and ions can also produce harmful effects on the body due to the toxicity of several types of metals. [16] For example, arsenic works as a potent poison due to its effects as an enzyme inhibitor, disrupting ATP production. [19]

Related Research Articles

In biology, homeostasis is the state of steady internal, physical, chemical, and social conditions maintained by living systems. This is the condition of optimal functioning for the organism and includes many variables, such as body temperature and fluid balance, being kept within certain pre-set limits. Other variables include the pH of extracellular fluid, the concentrations of sodium, potassium, and calcium ions, as well as the blood sugar level, and these need to be regulated despite changes in the environment, diet, or level of activity. Each of these variables is controlled by one or more regulators or homeostatic mechanisms, which together maintain life.

In cellular biology, active transport is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellular energy to achieve this movement. There are two types of active transport: primary active transport that uses adenosine triphosphate (ATP), and secondary active transport that uses an electrochemical gradient. This process is in contrast to passive transport, which allows molecules or ions to move down their concentration gradient, from an area of high concentration to an area of low concentration, without energy.

A period 4 element is one of the chemical elements in the fourth row of the periodic table of the chemical elements. The periodic table is laid out in rows to illustrate recurring (periodic) trends in the chemical behaviour of the elements as their atomic number increases: a new row is begun when chemical behaviour begins to repeat, meaning that elements with similar behaviour fall into the same vertical columns. The fourth period contains 18 elements beginning with potassium and ending with krypton – one element for each of the eighteen groups. It sees the first appearance of d-block in the table.

<span class="mw-page-title-main">Sodium–potassium pump</span> Enzyme found in the membrane of all animal cells

The sodium–potassium pump is an enzyme found in the membrane of all animal cells. It performs several functions in cell physiology.

<span class="mw-page-title-main">Metalloprotein</span> Protein that contains a metal ion cofactor

Metalloprotein is a generic term for a protein that contains a metal ion cofactor. A large proportion of all proteins are part of this category. For instance, at least 1000 human proteins contain zinc-binding protein domains although there may be up to 3000 human zinc metalloproteins.

<span class="mw-page-title-main">Mineral (nutrient)</span> Chemical element required as an essential nutrient by organisms to perform life functions

In the context of nutrition, a mineral is a chemical element. Some "minerals" are essential for life, most are not. Minerals are one of the four groups of essential nutrients, the others of which are vitamins, essential fatty acids, and essential amino acids. The five major minerals in the human body are calcium, phosphorus, potassium, sodium, and magnesium. The remaining elements are called "trace elements". They are iron, chlorine, cobalt, copper, zinc, manganese, molybdenum, iodine, and selenium.

<span class="mw-page-title-main">Trace metal</span> Metals subset of trace elements

Trace metals are the metals subset of trace elements; that is, metals normally present in small but measurable amounts in animal and plant cells and tissues and that are a necessary part of nutrition and physiology. Some biometals are trace metals. Ingestion of, or exposure to, excessive quantities can be toxic. However, insufficient plasma or tissue levels of certain trace metals can cause pathology, as is the case with iron.

<span class="mw-page-title-main">Calcium in biology</span> Use of calcium by organisms

Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction of all muscle cell types, and in fertilization. Many enzymes require calcium ions as a cofactor, including several of the coagulation factors. Extracellular calcium is also important for maintaining the potential difference across excitable cell membranes, as well as proper bone formation.

<span class="mw-page-title-main">Potassium in biology</span> Use of Potassium by organisms

Potassium is the main intracellular ion for all types of cells, while having a major role in maintenance of fluid and electrolyte balance. Potassium is necessary for the function of all living cells, and is thus present in all plant and animal tissues. It is found in especially high concentrations within plant cells, and in a mixed diet, it is most highly concentrated in fruits. The high concentration of potassium in plants, associated with comparatively very low amounts of sodium there, historically resulted in potassium first being isolated from the ashes of plants (potash), which in turn gave the element its modern name. The high concentration of potassium in plants means that heavy crop production rapidly depletes soils of potassium, and agricultural fertilizers consume 93% of the potassium chemical production of the modern world economy.

<span class="mw-page-title-main">Magnesium in biology</span> Use of Magnesium by organisms

Magnesium is an essential element in biological systems. Magnesium occurs typically as the Mg2+ ion. It is an essential mineral nutrient (i.e., element) for life and is present in every cell type in every organism. For example, adenosine triphosphate (ATP), the main source of energy in cells, must bind to a magnesium ion in order to be biologically active. What is called ATP is often actually Mg-ATP. As such, magnesium plays a role in the stability of all polyphosphate compounds in the cells, including those associated with the synthesis of DNA and RNA.

<span class="mw-page-title-main">Nucleoplasm</span> Protoplasm that permeates a cells nucleus

The nucleoplasm, also known as karyoplasm, is the type of protoplasm that makes up the cell nucleus, the most prominent organelle of the eukaryotic cell. It is enclosed by the nuclear envelope, also known as the nuclear membrane. The nucleoplasm resembles the cytoplasm of a eukaryotic cell in that it is a gel-like substance found within a membrane, although the nucleoplasm only fills out the space in the nucleus and has its own unique functions. The nucleoplasm suspends structures within the nucleus that are not membrane-bound and is responsible for maintaining the shape of the nucleus. The structures suspended in the nucleoplasm include chromosomes, various proteins, nuclear bodies, the nucleolus, nucleoporins, nucleotides, and nuclear speckles.

<span class="mw-page-title-main">Plant nutrition</span> Study of the chemical elements and compounds necessary for normal plant life

Plant nutrition is the study of the chemical elements and compounds necessary for plant growth and reproduction, plant metabolism and their external supply. In its absence the plant is unable to complete a normal life cycle, or that the element is part of some essential plant constituent or metabolite. This is in accordance with Justus von Liebig’s law of the minimum. The total essential plant nutrients include seventeen different elements: carbon, oxygen and hydrogen which are absorbed from the air, whereas other nutrients including nitrogen are typically obtained from the soil.

Inorganic ions in animals and plants are ions necessary for vital cellular activity. In body tissues, ions are also known as electrolytes, essential for the electrical activity needed to support muscle contractions and neuron activation. They contribute to osmotic pressure of body fluids as well as performing a number of other important functions. Below is a list of some of the most important ions for living things as well as examples of their functions:

<span class="mw-page-title-main">Electrolyte imbalance</span> Medical condition

Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, fluid balance, oxygen delivery, acid–base balance and much more. Electrolyte imbalances can develop by consuming too little or too much electrolyte as well as excreting too little or too much electrolyte. Examples of electrolytes include: calcium, chloride, magnesium, phosphate, potassium, and sodium.

Bioinorganic chemistry is a field that examines the role of metals in biology. Bioinorganic chemistry includes the study of both natural phenomena such as the behavior of metalloproteins as well as artificially introduced metals, including those that are non-essential, in medicine and toxicology. Many biological processes such as respiration depend upon molecules that fall within the realm of inorganic chemistry. The discipline also includes the study of inorganic models or mimics that imitate the behaviour of metalloproteins.

<span class="mw-page-title-main">Sodium in biology</span> Use of Sodium by organisms

Sodium ions are necessary in small amounts for some types of plants, but sodium as a nutrient is more generally needed in larger amounts by animals, due to their use of it for generation of nerve impulses and for maintenance of electrolyte balance and fluid balance. In animals, sodium ions are necessary for the aforementioned functions and for heart activity and certain metabolic functions. The health effects of salt reflect what happens when the body has too much or too little sodium. Characteristic concentrations of sodium in model organisms are: 10 mM in E. coli, 30 mM in budding yeast, 10 mM in mammalian cell and 100 mM in blood plasma.

A metal–air electrochemical cell is an electrochemical cell that uses an anode made from pure metal and an external cathode of ambient air, typically with an aqueous or aprotic electrolyte.

Metals in medicine are used in organic systems for diagnostic and treatment purposes. Inorganic elements are also essential for organic life as cofactors in enzymes called metalloproteins. When metals are scarce or high quantities, equilibrium is set out of balance and must be returned to its natural state via interventional and natural methods.

Evolution of metal ions in biological systems refers to the incorporation of metallic ions into living organisms and how it has changed over time. Metal ions have been associated with biological systems for billions of years, but only in the last century have scientists began to truly appreciate the scale of their influence. Major and minor metal ions have become aligned with living organisms through the interplay of biogeochemical weathering and metabolic pathways involving the products of that weathering. The associated complexes have evolved over time.

<span class="mw-page-title-main">Zinc in biology</span> Use of Zinc by Organisms

Zinc is an essential trace element for humans and other animals, for plants and for microorganisms. Zinc is required for the function of over 300 enzymes and 1000 transcription factors, and is stored and transferred in metallothioneins. It is the second most abundant trace metal in humans after iron and it is the only metal which appears in all enzyme classes.

References

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  2. 1 2 3 4 5 6 Maret W (2018). "Metallomics: The Science of Biometals and Biometalloids". In Arruda MA (ed.). Metallomics. Advances in Experimental Medicine and Biology. Vol. 1055. Cham: Springer International Publishing. pp. 1–20. doi:10.1007/978-3-319-90143-5_1. ISBN   978-3-319-90143-5. PMID   29884959. S2CID   46997332.
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  4. ↑ Aggett PJ (August 1985). "Physiology and metabolism of essential trace elements: an outline". Clinics in Endocrinology and Metabolism. 14 (3): 513–543. doi:10.1016/S0300-595X(85)80005-0. PMID   3905079.
  5. ↑ Cavalieri RR (April 1997). "Iodine metabolism and thyroid physiology: current concepts". Thyroid. 7 (2): 177–181. doi:10.1089/thy.1997.7.177. PMID   9133680.
  6. 1 2 3 4 5 6 7 Foulquier F, Legrand D (October 2020). "Biometals and glycosylation in humans: Congenital disorders of glycosylation shed lights into the crucial role of Golgi manganese homeostasis" (PDF). Biochimica et Biophysica Acta (BBA) - General Subjects. 1864 (10): 129674. doi:10.1016/j.bbagen.2020.129674. PMID   32599014. S2CID   220268697.
  7. 1 2 3 Shaul O (2002-09-01). "Magnesium transport and function in plants: the tip of the iceberg". Biometals. 15 (3): 307–321. doi:10.1023/A:1016091118585. ISSN   1572-8773. PMID   12206396. S2CID   32535554.
  8. 1 2 3 Cuajungco MP, Ramirez MS, Tolmasky ME (February 2021). "Zinc: Multidimensional Effects on Living Organisms". Biomedicines. 9 (2): 208. doi: 10.3390/biomedicines9020208 . PMC   7926802 . PMID   33671781.
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  10. ↑ Wilck N, Balogh A, Markó L, Bartolomaeus H, Müller DN (September 2019). "The role of sodium in modulating immune cell function". Nature Reviews. Nephrology. 15 (9): 546–558. doi:10.1038/s41581-019-0167-y. PMID   31239546. S2CID   195354083.
  11. 1 2 3 4 Wang M, Zheng Q, Shen Q, Guo S (April 2013). "The critical role of potassium in plant stress response". International Journal of Molecular Sciences. 14 (4): 7370–7390. doi: 10.3390/ijms14047370 . PMC   3645691 . PMID   23549270.
  12. ↑ Yamori M, Njelekela M, Mtabaji J, Yamori Y, Bessho K (2011-08-04). "Hypertension, periodontal disease, and potassium intake in nonsmoking, nondrinker african women on no medication". International Journal of Hypertension. 2011: 695719. doi: 10.4061/2011/695719 . PMC   3150144 . PMID   21826260.
  13. 1 2 Fasae KD, Abolaji AO, Faloye TR, Odunsi AY, Oyetayo BO, Enya JI, et al. (September 2021). "Metallobiology and therapeutic chelation of biometals (copper, zinc and iron) in Alzheimer's disease: Limitations, and current and future perspectives". Journal of Trace Elements in Medicine and Biology. 67: 126779. doi: 10.1016/j.jtemb.2021.126779 . PMID   34034029.
  14. 1 2 Nelson DL (2021). Lehninger Princples of Biochemistry. [S.l.]: W H Freeman. ISBN   978-1-319-38147-9. OCLC   1333920083.
  15. 1 2 3 Weinberg ED (February 1996). "The role of iron in cancer". European Journal of Cancer Prevention. 5 (1): 19–36. JSTOR   45074238. PMID   8664805.
  16. 1 2 Lippard SJ (1994). "Metals in Medicine". Bioinorganic Chemistry (PDF). pp. 505–83.
  17. ↑ AHFS Consumer Medication Information (2014). "Lithium". Medline. U.S. National Library of Medicine.
  18. ↑ Kean WF, Hart L, Buchanan WW (May 1997). "Auranofin". British Journal of Rheumatology. 36 (5): 560–572. doi: 10.1093/rheumatology/36.5.560 . PMID   9189058.
  19. ↑ Singh AP, Goel RK, Kaur T (July 2011). "Mechanisms pertaining to arsenic toxicity". Toxicology International. 18 (2): 87–93. doi: 10.4103/0971-6580.84258 . PMC   3183630 . PMID   21976811.
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