Despite that, there are more than 100 types of amino acids found in nature; only 20 of them are employed for protein synthesis. Among these 20 amino acids, excepting glycine, which does not display chirality, only the L-form of the 19 is used for protein synthesis. This is because ribosomes, where protein synthesis occurs, do not feature the utilization of D-form amino acids. As nothing in the universe exists in vain but with multiple tasks, D-amino acids have a job in the maintenance of life after protein synthesis in very different fashions. The way D-amino acids are employed in the execution and control of physiological preferences amazes scientists.

Up until recent times, D-amino acids were believed to be synthesized mostly by bacteria and plants, unlike mammals, and were considered dysfunctional as they passed, via consumption of nutrients, from bacteria and plants. However when D-amino acids were noticed for having roles as important as L-amino acids during the 1990s, the field gained significance. It was demonstrated that D-amino acids were found widely in invertebrates, vertebrates, and humans as free forms or inside proteins, undertaking critical functions in the nervous and endocrine systems. The most interesting point is the conversion of amino acids from the L-form into the D-form after the protein synthesis occurs in the peptides that are present in the venomous secretions of various animals. This conversion leads to the alteration of the peptide identity and function. Racemase and isomerase (epimerase) enzymes are utilized as they are created for this task. Usually, one or two amino acids of the D-form peptides are in D-form.

When chemist Gunther Kreil of the Austrian Academy of Sciences learned about the use of South American poisonous tree frogs (Phyllomedusa sauvagei ) during Shamanic hunting ceremonies by local Peruvian tribe (Matses), he studied this poison in detail. Participants of the ceremony first caused a burn on their chest region, then applied the poison they obtained from the frog skin over it. Diarrhea and tachycardia started within a minute, followed by a brief faintness. Once they recovered after a few minutes, they were to find themselves in a much more vigorous and exhilarated state of mind. The poison they were applying to their chest contained the dermorphin peptide, which has psychoactive, hallucinogenic effects and a D-amino acid. This peptide is a pain killer 30-40 times more effective than morphine. Among the 7 amino acids found in this peptide (heptapeptide), all are in L-form, except for one. Only the alanine, as the second in the peptide sequence, is in D-form and is produced via the isomerase enzyme from the L-alanine after the protein synthesis. G. Kreil discovered this D-form synthesizing enzyme in 2005. When this peptide was synthesized artificially in the laboratory, it did not display any biological activity or hallucinogenic effect. After a careful investigation of the case, it was found that frog skin based peptide had a D-form alanine second in its sequence; however, the one produced in laboratory had an L-form alanine. It was the presence of only one D-amino acid that made the difference in discovering the identity and function to the natural peptide in the poison.

In recent years dermorphin has started to be used as an illegal performance enhancer during horse races because of its pain killer feature. Horses on dermorphin can run longer and faster since they cannot feel the pain related to foot fatigue.

P. Kuchel of Sydney University also showed a D-amino acid presence in the peptide structured of the poison in the Platypus, a semiaquatic egg-laying mammal. Males use this poison as a weapon to fend off competitors. In 2009, Matthew Waldor and his friends at Harvard University discovered that the sugar-protein mix (matrix) called peptidoglycan found in the composition of bacterial cell walls is structured in a way to contain primarily D-alanine, D-methionine, and D-leucine. More interestingly, D-amino acids of the peptidoglycan structure were able to play a stimulatory role in coordinating the activities of other bacteria in the colony. For example, they acted as light houses in the use of florescence and helped in the formation of thin layers (bio-films) on various surfaces in bacteria. Once we understand the way D-amino acids help in communication between bacteria, it will be possible to use them as a drug. It’s possible they can be used to disintegrate bacteria that forms on teeth, in the lungs of cystic fibrosis patients, on clogs in fuel lines and water tanks, and in medical devices such as catheters.

D-amino acid containing peptides found in lobsters help maintain salinity levels and facilitate courtship in mating seasons. In recent years, D-amino acid containing antimicrobial peptides were discovered (bombinines) in the secretion glands of fire-bellied toad skins (Bombina sp). In this peptide, the second amino acid was in the D-form (D-allo-isoleucine). Two different peptides were found containing D-amino acids in the second position of the amino acid sequence of the poison secreted by Platypus males.

One of the reasons for D-amino acids to exist in animal poisons is that peptides containing D-Amino acids can not be easily degraded by the proteases (peptide bond breaking enzyme) of the host or opponents. Even though proteases can quickly and easily digest proteins composed of L-form amino acids, they struggle to do so with peptide bonds between D and L form amino acids. Pharmaceutical companies are trying to add D-amino acids to the peptide-structured drugs to prevent the quick degradation of peptides and proteins used for treatments when ingested. However, the addition of a D-form amino acid brings the high possibility of a situation that changes the function of a peptide or protein, or causes the loss of a protein. Nonetheless, specialists in this field point out that at least some amount of the D-amino acids that are produced by trillions of bacteria found on the skin, in the digestive track, and among other parts of the body can still be utilized for human health and convenience.

The D-serine of the mammalian nerve systems (glial cells and neurons), the D-aspartate of the neuro-endcorine, endocrine tissues, and testicles, and the D-alanine and D-aspartate amino acids of aquatic animals are abundant. D-Serine in the brain is synthesized by the conversion of L-serine into D-serine by the serine racemase enzyme. D-aspartate is in charge of hormone synthesis and secretion, and the regulation of spermatogenesis, and is produced by aspartate racemase and degraded by D-aspartate oxidase. It is also predicted to play role in the synthesis of hormones such as melatonin and testosterone.

As of now, four enzymes have been detected to be in charge of D-amino acid metabolism in mammals. How these are controlled is still unknown.

Publications pertaining to the association of epilepsy, schizophrenia, and bipolar disorders with enzymes in charge of D-amino acid synthesis and break down have increased in recent years. From this point of view, serine racemase and D-amino oxidase can be used to develop new potential drugs regarding the treatment of similar NMDA receptor associated diseases.

The first data demonstrating the use of D-amino acids in saliva in organs outside of the human brain was obtained by Y. Nagata and his team at the University of Nihon, Tokyo. A team led by Kenji Hamase of the Kyushu University discovered high levels of D-alanine storage in the beta cells of the rat pancreas. Kuchel, who discovered the enzymes converting the L-amino acids in to D forms in duck-billed Platypus poison, also found similar enzymes in the hearts of mice and humans. According to Kuchel, the physiological roles of those in humans remain to be unknown.

As a result, the common feature of toxins and antimicrobial peptides that are produced and secreted by animals is to contain D-amino acid. These peptides can be the source of a potential drug in the treatment of diseases such as cystic fibrosis, schizophrenia, and macular degeneration of the eye.

These prove that, especially in biology, exceptions are common; life is enriched via examples of extraordinary lives, processes, and mechanisms in unexpected places by unpredictable molecules or interesting reactions that can’t be predicted. Such discoveries help deepen our wonder at the intricacy and wisdom of creation.

Nanoscience and nanotechnology started off in the early 1980s when scientists were able to detect materials on the nano-level through microscopic systems. This development enabled the synthesis of nano-level materials such as carbon nanotubes, nano crystals, and metal oxide nanoparticles. Nanotechnology is a type of technology, resulting from the research conducted on the atomic, molecular and macromolecular levels. A nanometer is one-billionth of a meter. Nano-level studies are conducted with materials whose sizes range between one to a hundred nanometers. Studies on the nano-level are conducted in the contemporary science fields such as chemistry, materials science, physics, biology, etc. One of the most compelling reasons that renders the research with nano-level materials so significant is that nanoparticles reflect a lot more different characteristics than when they do at the macro-level. Due to their small sizes, nanoparticles, especially those under 20 nm, have magnificent optical, magnetic, and chemical properties.[1] Nanoparticles include much more energy than the macro-level materials; this is because the ratio of the surface area of nanoparticles to their volume is much more bigger than the ratio in macro-level materials. A significant amount of energy is stored in nanoparticles as free surface energy. This energy revealed on the nano-level not only increases the reactivity of iron nanoparticles (the propensity to chemical reactivity), but also renders the magnetic qualities of materials quite differently than they would be at the macro-level.

Many types of nanoparticles are widely used in our daily lives. Iron, gold, silver and cadmium sulphide nanoparticles are some of the most commonly investigated nanoparticles. Yet iron nanoparticles receive special attention from scientists essentially in the field of biotechnology. Iron nanoparticles demonstrating different magnetic features have a wide range of use in fields, including but not limited to health care and electric/electronic industry. Owing to its magnetic feature, iron is also used in magnetic recording. The production of needle-shaped iron nanoparticles with high magnetic features has facilitated the manufacturing of mobile electronic devices with a high recording capacity. In this paper, we will focus on the use of iron nanoparticles’ contribution to the advances in the field of biotechnology, among numerous other contributions of iron nanoparticles in other fields.

Nanobiotechnology

Nanobiotechnology, among other fields of nanotechnology, is the field that focuses on biological systems. Nano-level devices designed to work with biosystems, nano-level cell biology, cell and nanoparticle interactions are some of the applications used in nanobiotechnology. Through those applications, biochemical processes and reactions in living beings can be scrutinized in great detail, which, in turn, enables scholars to come up with innovations in both diagnosis and treatment of various illnesses.

The following are the primary application areas of magnetic nanoparticles in the field of bionanotechnology: development of magnetic resonance imaging systems, and cancer research. Especially, iron oxides (magnetite, Fe3O4, maghemite, Fe2O3), owing to their cohesion with the chemical structure of biological systems, are prevalently used in biotechnology.

Magnetic Resonance Imaging (MRI)

MRI, mostly used in the medical field, is the method to monitor the internal structure of living mechanisms. Through the magnetic area and radio frequency waves, the image of a living tissue is formed. MRI is a complex system that produces images based on the intensity and movements of hydrogen atoms in the tissue. The MRI technique is used to diagnose almost all sorts of illnesses today. Yet it is most frequently used with illnesses pertaining to the central nervous system, brain and spinal cord. It has also been used to diagnose muscle-related and skeleton-related medical conditions, such as meniscus and herniated disc symptoms, as well as all types of neurological illnesses. MRI has not been found detrimental to any living organism thus far.

It is the paramagnetic ions such as gadolinium that are most frequently used as contrast enhancement agents in MRI applications. Although gadolinium has a high moment, this moment is too low compared to superparamagnetic materials. For this reason, superparamagnetic iron oxide nanoparticles are known to be more efficient MRI contrast enhancement agents. Known as such, those iron oxide nanoparticles are quite advantageous over gadolinium. Those nanoparticles can easily be functionalized to interact with biological samples. For example, superparamagnetic nanoparticles, which are not normally taken up by cells efficiently, can do so after being covered with another material (e.g. Dextran) that can ordinarily go into a cell. Thus, MR images of particular tissues could be obtained clearly, which enables us to make more accurate diagnoses and treatments.

Iron oxide nanoparticles are also deemed to be an efficient potential future method in cancer treatment. The results of several studies conducted to fulfill this goal are encouraging.

Iron oxide superparamagnetic nanoparticles are being tested as a method in hyperthermia treatment. Hyperthermia is defined as an abnormally high body temperature, and its treatment is carried out through the removal of certain tissues by increasing its temperature up to (42–46) 0C for 30 minutes. For instance, cancer infected liver tissues are exterminated through the hyperthermia method, which sends biologically activated iron oxide nanoparticles to those infected tissues. Moreover, none of the healthy tissues are damaged during this process. You may find more detailed information in references [1, 2, 4, 6] on how nanoparticles are aptly sent to the cancer infected tissues only while the surrounding healthy tissues remain unaffected by them. Hundreds of researchers carry out experiments and publish their findings on this topic everyday. Yet, further research needs to be done in order to reach solid conclusions.

Iron, which seems to carry greater potential significance than we previously thought, should receive much attention from scholars due to the fact that a chapter (surah) in the Holy Qur’an is entitled “Iron” (Hadeed). The question is, why was a 29-line chapter in the Qur’an is called (Iron) when the word “iron” was only mentioned once throughout the entire chapter.

The chapter “Iron” first begins by drawing the reader’s attention to the attributes and praised names of God. It invites people to believe in God and his messenger Muhammad (peace be upon him) by exalting God as the Almighty, Sovereign, Ruler, One whose existence is without a beginning and an end, Manifest and Hidden. Then, the chapter goes on to encourage believers to donate their wealth for the sake of God, for those who follow the word of God are rewarded with a place in Heaven. It also advises believers never to lose their ardor, while reminding them that even the earth will be resurrected after all has perished. And the wisdom behind the creation of iron is explained as such:

Assuredly We have sent Our Messengers with manifest truths (and clear proofs of their being Messengers), and We have sent down with them the Book and the Balance so that (relations among) humankind may live by equity. And We have sent down iron in [the essence] which is stern might and benefits for humankind, so that God may mark out those who help (the cause of) God and His Messengers, though they do not see Him. Surely God is All-Strong, All-Glorious with irresistible might. (57:25)

This particular verse includes several remarkable points. First, the very use of the phrase “sending down” for iron is so striking that it was also mentioned in [3, 5]. Another perplexing statement is, We sent down iron in [the essence] which is stern might and benefits for humankind, which might pave the way for thought-provoking venues regarding nanotechnology. The verse also indicates that which makes iron so special, its indiscernible or hidden qualities, rather than the outer surface of it. The specific reference to the “essence” of iron hints at this point. If the message of the verse had been related to the external qualities of iron, then the choice of the words would differ accordingly. Since the Qur’an is the word of God, there is wisdom behind the selection and sequencing of each word and letter. From this point of view, we can interpret that this verse informs us about the significance of the essence of iron on the nano level.

The significance of iron as stated in a single verse of the Qur’an has been briefly discussed. Numerous studies on the use of iron in nanotechnology seem to be on the horizon, which will only contribute to our admiration for the miracle of the Qur’an.

Kamil Ezgin is pursuing a PhD degree in chemistry in USA. For correspondence with the author kamilezgin@gmail.com.

References

1. Dale L. Huber. Synthesis, Properties, and Applications of Iron Nanoparticles, small, 2005, 1, No. 5, 482-501.
2. An-Hui Lu, E.L. Salabas, and Ferdi Schuth, Magnetic Nanoparticles: Synthesis, Protection, Functionalization, and Application, Angew. Chem. Int. Ed. 2007, 46, 1222-1244.
3. Edib Masûkî. “Enteresan Bir Tespit: Demirin Sakladiði Sir,” Sizinti, 1985, No. 73.
4. Peter Majewski and Benjamin Thierry. “Functionalized Magnetic Nanoparticles- Synthesis, Properties, and Bio-Applications,” Critical Reviews in Solid State and Materials Sciences, 2007, 32, 203-215.
5. http://www.mergeous.com/bullet.asp?tag=72
6. Volker Mailander and Katharina Landfester, “Interaction of Nanoparticles with Cells,” Biomacromolecules 2009, 10, 2379–2400.