A new article with our undergraduate student: Current Knowledge on Tumour Markers in Veterinary Oncology

tumor_markers

The review article entitled “Current Knowledge on Tumour Markers in Veterinary Oncology”, in which Gamze Bilgili is the lead author, one of our NEU Faculty of Veterinary Medicine students was published in the journal “AS ​​Veterinary Sciences (ISSN: 2582-3183)”.


Bilgili G, Alpay M, Ceylanli D, Gençosman S, Gültekin Ç, Şehirli AÖ, Sayiner S. (2022). Current Knowledge on Tumour Markers in Veterinary Oncology. Acta Scientific Veterinary Sciences, 4(2): 37-45. DOI: 10.31080/ASVS.2022.04.0306


We aimed to compile and present tumour markers that have been evaluated and are being studied in veterinary medicine.

Tumour markers are molecules that are produced by tumour cells or an organism in response to the presence of a tumour. These molecules can be found in blood, urine, tissues, and body fluids, and blood levels are the most commonly tested. Tumour markers are particularly useful in aiding diagnosis, assessing disease progression, and monitoring treatment.

Tumour markers are an exciting field of study for both veterinary and human medicine. We hope our article will be beneficial. 

Click to access the article.

Chronic Kidney Disease in Dogs: A New Approach to Assess and Monitor Inflammation and Oxidative Stress

köpekler

According to a recent study, a specially formulated nutrient supplement was added to the diet and promising results were determined in monitoring advanced chronic kidney disease in dogs.

Chronic Kidney Disease (CKD) causes irreversible loss of kidney function and is often considered a disease of senior adult animals. The severity of this disease is divided into different stages (1-4) according to the International Renal Interest Association (IRIS). Even if radical treatment is not possible,  conventional and alternative treatment methods are used. Besides, diet adjustments and periodic laboratory tests are made to follow and hold the disease under control.

kronik-yetmezlik, kidney

The results of the research carried out by Elisa Martello and her team to test a new nutritional supplement for the control of the disease were published in the journal Veterinary Sciences (Impact factor = 2.304), a journal of the very prestigious MDPI. In the study, which included 30 dogs with CKD, the animals were divided into two groups. They added 15 different nutritional supplements with a special formulation that they prepared in addition to a commercial kidney diet to one and a commercial kidney diet to the other. These included Lactobacillus acidophilus D2/CSL, Olea europaea L. extract, chitosan, calcium lactate-gluconate and fructooligosaccharides. The animals were fed in accordance with the study procedure for 90 days, and at the end, clinical examinations and laboratory analyses were made, and the results were evaluated.

According to the results of the researchers, it was determined that creatinine values, which is a critical marker of kidney disease, decreased significantly in the group that took the nutritional supplement they prepared.

The mean creatinine value, which was 3.17 mg/dL at the beginning, decreased to 2.4 mg/dL at the end of the study. There was no significant change in the group that did not take the nutritional supplement. Similarly, blood urea nitrogen (BUN), phosphorus (P), symmetrical dimethylarginine (SDMA), urine protein:creatinine ratio (UPC), c-reactive protein (CRP-inflammation marker) and reactive oxygen metabolite derivative compounds (d-ROM) values ​​were also found to decrease in the group that received nutritional supplements. In this sense, the regression of oxidative stress can be considered an important result. It is known that oxidative stress directly contributes to the progression of CKD by causing tissue damage and inflammation.

The researchers also emphasized that their results covered a small sample group and most animals with third-stage CKD. In other words, the study data represented a limited group. This type of study needs to be improved by performing a larger study that includes both a larger population of dogs and different analysis parameters. Researchers emphasised this situation and actually opened a new door.

As a conclusion of the study, it was stated that this new nutritional supplement may be a good approach to controlling metabolic, inflammatory, and oxidative processes in animals with advanced CRF.


Further reading: Martello E, Perondi F, Bruni N, Bisanzio D, Meineri G, Lippi I. Chronic Kidney Disease and Dietary Supplementation: Effects on Inflammation and Oxidative Stress. Vet Sci. 2021 Nov 15;8(11):277. doi: 10.3390/vetsci8110277. PMID: 34822650.

Association of certain foods with heart disease in dogs: A Foodomics study

golden retriever

A recent foodomics study reported that the presence of legumes such as peas or lentils in the diet may contribute to the development of dilated cardiomyopathy in dogs.

Dilated cardiomyopathy (DCM) is the most common heart disease in dogs. This disorder causes the chambers of the heart to enlarge and pump blood less effectively. So, dogs may face congestive heart failure or unexpected death.

Historically, it is known that the disease mainly affects large breed dogs and Cocker Spaniels. However, in 2018, United States Food and Drug Administration (FDA) officials reported that they began receiving reports of DCM regarding dogs of other breeds as well. Additionally, in 2020, the FDA said it had received approximately 1,100 reports of adverse events linked to DCM since January 2014 and plans to collaborate with researchers on studies of non-hereditary DCM, including its possible link to diet.

FDA representatives reported that more than 9 out of 10 dogs with DCM identified in the reports were fed diets rich in peas, lentils, or both, and in this regard, a study was initiated to evaluate the association between nine diets associated with dogs with DCM.

Studies involving the discovery and comparison of biochemical compounds in foods, similar to studies on all metabolites in body fluids or tissues (metabolomics), are defined as “foodomics” and is an important field of study today; in other words, the metabolomic approach to food. Therefore, researchers identified, measured and compared the concentrations of 830 biochemical compounds in foods in diets in order to shed more light on the link between diet and the development of disease.

mercimek, lentil, heart
bezelye, pea, heart

Researchers have found that diets associated with DCM have lower levels of B vitamins related to cardiac metabolism and synthesis of carnitine and taurine. Additionally, diets associated with DCM also have higher concentrations of amino acids, amino acid derivatives, and plant-derived compounds; suggested that some of these may contribute to deficiencies in molecules essential for cardiac function by affecting carnitine metabolism. On the other hand, given that dietary taurine deficiency in cats is a cause of DCM, when researchers examined its concentration in different feeds, they found no significant taurine-related differences for dogs.

In conclusion, some components were identified that contributed to the biochemical differences between diets. Peas and, to a lesser extent, lentils appear to be major sources of high concentrations of certain biochemical compounds in diets associated with DCM. Although researchers cannot definitively determine whether any of these compounds and components are the cause of the disease, their findings indicate that peas may be the main component associated with dietary DCM in dogs.


Further reading: Smith, C.E., Parnell, L.D., Lai, CQ. et al. Investigation of diets associated with dilated cardiomyopathy in dogs using foodomics analysis. Sci Rep 11, 15881 (2021). https://doi.org/10.1038/s41598-021-94464-2

Yoga may be beneficial for MS patients

Multiple Sclerosis is accepted as the most common Central Nervous System (CNS) disease worldwide and is among the autoimmune diseases group.

Multiple Sclerosis (MS) disease has a complex aetiology and although there are many studies, its cause cannot be fully explained. It is believed to occur through the interaction of genetic and environmental factors. When low serum vitamin D levels, ultraviolet rays, smoking, childhood obesity and Epstein-Barr virus infection are evaluated together with the genetic history of the individual, it is shown that these causes play a major role in the development of the disease. In addition, it is important to improve the quality of life of these MS patients, and yoga has been studied in this sense.

ms, yoga, myelin sheath
In MS, the immune system attacks the protective sheath (myelin) that covers nerve fibres, causing communication problems between the brain and the rest of the body.

Nerve cells have protective sheaths that surround them, called myelin sheaths. In MS disease, the immune system of the individual cannot identify his own nerve cells and tries to destroy them, causing damage and/or destruction of the myelin sheaths called demyelination. As a result, CNS inflammation occurs. As a result, nerve cells are damaged and the nerve transmission is damaged. Various nervous system disorders occur as a result of damage to these nerve fibres, which are located in the white matter of the CNS and enable information exchange with other cells of the body. Double vision or blindness, incoordination, muscle weakness, numbness/tingling in the face or body, chronic pain and fatigue are among the common symptoms. These symptoms differ from individual to individual. Changes in mood and sleep problems are also common symptoms after an MS diagnosis.

MS patients are advised to eat healthily and act under the control of experts, and examine their own body, mind and emotional state as a whole while performing the movements. Thus, the individual will choose what is good for him with awareness and will try to minimize the aggressive course of the disease with self-awareness. For these reasons, the connection of MS disease with the philosophy and practice of Yoga has gained importance, especially in recent years, and the number of scientific studies on this subject is increasing day by day.

YOGA: A supportive approach to MS patients

Yoga is derived from the Sanskrit word “Yuj”. The word yuj means oneness of body, mind and spirit, which means unity, devotion.

yoga

Yoga is a traditional method that originated in India over 5000 years ago. There are different types of yoga today. The underlying principle of all types of yoga is the same and consists of the forms of Asana (physical posture), Pranayama (breathing techniques), Dhayana (meditation).

Yoga in general; preserving its traditional form and philosophy, it is applied to develop mental and physical strength, endurance, flexibility, calmness and a sense of harmony. All postures are practiced by observing the body and mind. This allows the individual to observe and develop himself/herself as a whole with awareness.

The effect of yoga on individuals with MS has been examined from the past to the present.

Vasudeva ve arkadaşlarının (2020)

In the study of Vasudeva et al. (2020); The history of each MS patient was examined and the program was created as a group. In addition to the asanas, the traditional form of yoga was preserved, and speaking the philosophy of yoga, breathing techniques, relaxation and meditation were included in the program. Certain sections from the book “Patanjali’s Yoga Sutras” have been selected and included in the program so that the patient can better synthesize himself in terms of pain and accept himself. This book was written by Patanjali, a sage. It is a book written in India between 500 and 400 AD and contains information about yoga from very ancient traditions. The daily routines (such as sleep patterns, and eating habits) of the patients participating in the program were arranged and also; A plant-based diet was recommended to patients. At the end of the study, the patient’s energy levels, pain states, balance in physical movements, strength and flexibility, self-confidence, urinary incontinence, sleep states, and changes in digestive and emotional states were examined. Positive results were obtained in all parameters examined and no side effects were reported.

In the study of Cohen et al. (2017); Yoga philosophy, breathing techniques and meditation were also included in the program along with asanas, and MS patients started a regular yoga program for eight weeks, twice a week. At the end of the program, each patient’s quality of life, mental status and physical condition were examined. It has been observed that the positive change in the mood of the individual increases the quality of life of the patient together with physical strengthening. No undesirable effects were reported.

In general, the purpose of all studies; The aim was to systematically evaluate and meta-analyze data on the efficacy and safety of yoga in improving health-related quality of life, fatigue, mobility, mood, and cognitive function in MS patients.

As a result, it has been reported that patients become more observant about their own moods and can change their reactions to daily situations consciously. Moreover; male patients reported that their families observed changes in mood and provided more support and encouragement. Overall, all patients reported that lifestyle changes and improved quality of life helped them.

Smile more at life with more Yoga. 🙂


Further reading

  • Alphonsus KB, Su Y, D’Arcy C. The effect of exercise, yoga and physiotherapy on the quality of life of people with multiple sclerosis: Systematic review and meta-analysis. Complement Ther Med. Published online 2019. doi:10.1016/j.ctim.2019.02.010
  • Cohen ET, Kietrys D, Fogerite SG, et al. Feasibility and Impact of an 8-Week Integrative Yoga Program in People with Moderate Multiple Sclerosis-Related Disability: A Pilot Study. Int J MS Care. 2017;19(1):30-39. doi:10.7224/1537-2073.2015-046
  • Cramer H, Lauche R, Azizi H, Dobos G, Langhorst J. Yoga for multiple sclerosis: a systematic review and meta-analysis. PLoS One. 2014;9(11):e112414. doi:10.1371/journal.pone.0112414
  • Dobson R, Giovannoni G. Multiple sclerosis – a review. Eur J Neurol. 2019;26(1):27-40. doi:10.1111/ene.13819
  • Dunne J, Chih HJ, Begley A, et al. A randomised controlled trial to test the feasibility of online mindfulness programs for people with multiple sclerosis. Mult Scler Relat Disord. Published online 2021. doi:10.1016/j.msard.2020.102728
  • Fasczewski KS, Garner LVM, Clark LA, Michels HS, Migliarese SJ. Medical Therapeutic Yoga for multiple sclerosis: examining self-efficacy for physical activity, motivation for physical activity, and quality of life outcomes. Disabil Rehabil. Published online 2020. doi:10.1080/09638288.2020.1760364
  • Field T. Yoga research review. Complement Ther Clin Pract. Published online 2016. doi:10.1016/j.ctcp.2016.06.005
  • Gannon S, Life D. Jivamukti Yoga: Practices for Liberating Body and Soul. Ballantine Books; 2002.
  • Skarlis C, Anagnostouli M. The role of melatonin in Multiple Sclerosis. Neurol Sci. Published online 2020. doi:10.1007/s10072-019-04137-2
  • Thakur P, Mohammad A, Rastogi YR, Saini R V., Saini AK. Yoga as an intervention to manage multiple sclerosis symptoms. J Ayurveda Integr Med. Published online 2020. doi:10.1016/j.jaim.2019.04.005
  • Vasudevan S, Devulapally S, Chirravuri K, Elangovan V, Kesavan N. Personalized Yoga Therapy for Multiple Sclerosis: Effect on Symptom Management and Quality of Life. Int J Yoga Therap. Published online 2020. doi:10.17761/2021-d-19-00037
  • Young HJ, Mehta TS, Herman C, Wang F, Rimmer JH. The Effects of M2M and Adapted Yoga on Physical and Psychosocial Outcomes in People With Multiple Sclerosis. Arch Phys Med Rehabil. Published online 2019. doi:10.1016/j.apmr.2018.06.032

The question of how spiders build webs has been answered.

Johns Hopkins University researchers have uncovered exactly how spiders build webs, using night vision and artificial intelligence to track and record every movement of their eight legs as they work in the dark.

A new understanding has been revealed of how spiders can create webs, and structures of such grace, complexity and geometric precision by these magnificent creatures. The results of the researchers’ study were published in the high-impact (2020 Impact Factor=10.834) journal of Cell Press, a respected publishing house, called Current Biology.

spider, web, spider web, spiders

Andrew Gordus, the senior author of the study, said: “I first started this topic while birding with my son. After seeing a magnificent net, I thought, ‘If you went to a zoo and saw a chimpanzee doing this, you would think it was an amazing and impressive chimpanzee.’ This is even more surprising because “A spider’s brain is so small, and I’m frustrated that we don’t know more about how this unusual behaviour occurs. We’ve now described the choreography of web formation that has never been done in such fine resolution for any animal architecture.” this made a statement.

Spiders, which blindly construct webs using only their sense of touch, have fascinated people for centuries. Andrew Gordus explained that the first step to understanding how the relatively small brains of these animal architects support high-level construction projects is to systematically document, analyze and record actions related to behaviours and motor skills that have never been done before.

In their study, the research team used a spider species (Uloborus diversus) native to the western United States that is small enough to fit comfortably on a fingertip. He designed a lab environment with infrared cameras and lights to observe the spiders during their nocturnal web-building work.

spider, spider web, web, spiders

With this setup, they tracked and recorded six spiders as they formed their webs each night. They tracked and documented millions of individual leg movements with machine vision software explicitly designed to detect limb movement.

The researchers found that their web-forming behaviour was quite similar among spiders, such that they were able to predict the part of the web that a spider is working on by simply seeing the position of one leg.

“Even though the final structure is slightly different, the rules they use to build the network are the same. They all use the same rules, which confirms that the rules are encoded in their brains. Now we want to know how these rules are encoded at the level of neurons.”

Abel Cover, a lead author of the study, said: “The spider is fascinating because here you have an animal with a brain built on the same basic building blocks as ours, and this work could offer clues to how we might understand larger brain systems, including humans, and I think it’s very exciting. ” made the statement.

Study authors included Nicholas Wilkerson, a former John Hopkins undergraduate and now a graduate student at Atlantic Veterinary College, and Jeremy Miller, a graduate student at Johns Hopkins.


Further Reading: Abel Corver, Nicholas Wilkerson, Jeremiah Miller, Andrew Gordus. Distinct movement patterns generate stages of spider web building. Current Biology, 2021; DOI: 10.1016/j.cub.2021.09.030

Source: Johns Hopkins University. “Spiders’ web secrets unraveled: Researchers document every step of spider-web building.” ScienceDaily. www.sciencedaily.com/releases/2021/11/211101105356.htm (accessed November 9, 2021).

The Importance of Chirality in Biological Systems

The existence of molecular chirality in the substances in the universe and the stereoisomer properties of molecules with stereogenic centres have been very influential in the development of organic chemistry and related sciences. The reason why chirality is important as biological activity is that molecular symmetry dominates biological events.

Although chirality is not essential for bioactivity, there are great differences in the activities of enantiomers in bioactive molecules with stereogenic centres such as drugs, flavourings, and food additives. The molecular components of living organisms are mostly chiral and these molecules have a dominant role in their interaction with bioactive substances. Receptors or free nerve endings enable all living systems to recognize and perceive all changes in the external environment they live in, such as chemical, physical, electrical, etc. that occur in their internal environment. Regardless of their functions in organisms and structures, the common point of all receptors is that they all consist of chiral molecules. Amino acids, DNA, carbohydrates and enzymes are the basic chiral structures found in living things. It is desired that the receptors behave differently in binding to the stimulant molecules, that is, they are enantioselective. For this reason, the synthesis of active substances with chirality characteristics is important because they are pharmaceutical raw materials. In drugs, one of the enantiomers exhibits desirable behaviours and beneficial pharmacological properties, while the other enantiomer may exhibit harmful pharmacological properties in general.

Today, pure compounds with enantiomeric behaviour are needed more than ever for the production of drugs and nutritional additives used in human, animal and plant health, and for the development of material science and industry such as liquid crystal and polymer. When the structures of living things and their activities were investigated, it was determined that since single isomers are target-selective in terms of biological effect, both enantiomers of the optically active substance are stronger and more reliable than having the same amounts in a mixture (racemic). As a result, it has been focused on the development of drugs consisting of a single enantiomer with a single isomer of the active substance. While one of the enantiomers in the racemic mixture of drugs with chiral compounds is physiologically beneficial, the other enantiomer can cause serious harm. Therefore, the definition of chiral structures in the pharmaceutical industry is very important. For all these reasons, the need for the development of new asymmetric synthesis methods has increased. Thus, studies on this subject have gained momentum in recent years.

Stereochemistry

The branch of science that examines the bonding structures of atoms in the molecule and their arrangement in space in three dimensions is called stereochemistry. He studies how atoms are arranged in their relative positions in space. Isomerism is a discipline that studies the arrangement of molecules in space. Isomers are two or more different chemical compounds that have different bonding structures between their atoms but can be represented by the same molecular formula. These are compounds that have the same molecular formula but different arrangements of atoms. At the same time, the chemical properties of isomer compounds are also different.

isomer, stereoisomer, conformational, configuration, optical isomerism, chirality
– Basic classification of isomers

Stereoisomers

The covalent bonds and functional groups of a biomolecule are very important in the function of that molecule. The three-dimensional form of the molecule is formed by atoms. Carbon compounds exist in the form of stereoisomers. Their atomic numbers are the same, but their arrangement in space is different, and they also show different physical properties. Molecular interrelationships between biomolecules are invariably stereospecific, which creates specific stereochemistry in the molecules. The arrangement of atoms is called configuration, these can be cis, trans configurations, or configurations of optical stereoisomers. These are referred to as three-dimensional structures in stereochemistry. A carbon atom is asymmetric with 4 different atoms or groups. A molecule containing one or more asymmetric carbons is also asymmetric.

Enantiomers cannot be converted to each other. This is because enormous energies are required to break the covalent bonds and displace the atoms. Enantiomers have the same chemical properties as long as they are not in non-chiral environments. For example, there are two enantiomers of alanine, an amino acid, and their physical properties such as melting point, boiling point and solubility are the same, but if the enantiomers are mixed, the physical properties of the product such as melting, freezing point and solubility will be different, but their chemical properties will not change. If the ratio of enantiomers in a mixture is desired, the chromatographic and spectroscopic properties change by showing an externally asymmetric effect. Thus, the enantiomers act differently from each other and their analysis is done.

– Molecular structures of L- and D- Alanine (Eren et al. 2017).

Enantiomers

It is an asymmetric mirror image of the optically active substance (chiral substance) and has two enantiomers. It is formed by the bonding of the chiral molecule to four different groups or the carbon group of the atom with σ-bonds. Although the carbon atom is the asymmetric centre of the molecule, such molecules have a pair of stereoisomers with different spatial structures. They do not conflict with mirror images. Their optical rotation angles are the same in numbers but opposite in sign. The melting and boiling points, densities, and all physical properties of the two symmetric enantiomers are similar. Their chemical properties are the same in non-chiral environments, they react at a similar rate and form to form similar substances. Optical rotation angles are the same numerically but opposite in sign. It is possible to separate them from each other with advanced chemical analysis methods. Since most living molecules are enantiomers, there is an obvious difference due to the effects of the two symmetric enantiomers on living things, including humans.

lactic acid, stereogenic
– Enantiomeric forms of lactic acid (Casalini et al. 2019).

One of the physical properties of enantiomers is that the polarized beam has the ability to rotate the vibrational plane. For this reason, enantiomers are also called optical isomers. One of the optical isomers rotates the propagation of the polarized beam to the right, and the other to the left. Normal light emanating from a single source is a vibratory phenomenon that oscillates (spreads) in all directions and in all planes. Wave motion follows a path perpendicular to the direction of the light. Polarized light is light that vibrates in a single perpendicular plane and is free of wave vibrations. Enantiomer (symmetric) molecules make a definite spin when they encounter light, and when their mirror images are in the opposite direction, the spin is balanced and the spin of the light is reset. The net rotation of a single non-mirrored enantiomer in solution is not reset. Therefore, the rotation of polarized light is reset to zero in racemic mixtures. The specific rotation angles of optically active substances can be measured with a polarimeter. The enantiomer that rotates the vibrational plane of polarized light to the right is called dextrorotatory, or the enantiomer that rotates to the right, and the enantiomer that rotates to the left is called levorotatory or left-handed.

Chirality

Chirality is a geometric property. If we explain this with an example from daily life if an item does not coincide with its mirror image, it is chiral, and if it coincides with its mirror image, it is not chiral. The characteristic of the chirality molecule is that the mirror image of the arrangement of the atoms of the molecule in space does not overlap. The chiral molecule has an asymmetric centre. Besides single chiral, there are chiral with more than one asymmetric centre. These are called multichiral structures. A molecule, however, may not exhibit chiral properties. Even if four different groups are attached to the sp3 hybridized carbon atom in a compound, it is chiral. If the asymmetric carbon atom is the centre of 4 different atoms or groups of atoms, it is called a stereogenic centre. Chiral compounds are asymmetric molecules due to the absence of an intramolecular symmetry plane and have two configuration isomers whose mirror images do not overlap each other. These two isomers are called enantiomers and these structures are enantiomeric to each other.

enantiomer, kiralite
– Two enantiomers of a chiral generic amino acid

Nomenclature and properties of chirality

The R and S rules, or Chan-Ingold-Prelog (CIP), is used to name two enantiomers with opposite configurations. This naming is done within the framework of some rules. Simply put the smallest group is placed behind the stereogenic carbon atom and the remaining three groups are decided based on their order of precedence by looking at their right (R) or left (S) orientation. However, in the event that a decision cannot be made with this rule, and if the first bonded atom is the same, the atoms that continue in the second or third order are examined and a decision is made.

After passing through the chiral molecules, plane-polarized light ceases to be a plane, rotates and forms an angle. This is called optical activity. On one side the angle becomes +α° (clockwise) and on the other side, the angle becomes -α° (counterclockwise). For example, at the same concentration and experimental conditions (S)-carvone rotates plane-polarized light +10° clockwise, while (R)-carvone rotates plane-polarized light -10° counterclockwise.

chiral, achiral, compounds
– Interactions of chiral and achiral compounds with plane-polarized light

The biological significance of chirality

The existence of chiral molecules and the existence of molecules with stereogenic centres have also made great contributions to organic chemistry and other branches of organic chemistry.

Chirality is not required for biological activities to occur, but the enantiomeric activity of biologically active molecules with stereogenic centres is different. For example, it is found in biologically active substances such as food additives, fragrances and flavours, pesticides, herbicides and medicines. Living organisms contain largely chiral molecules in their components, and these chiral molecules play a dominant role in the mutual action of bioactive substances. All physical, chemical, and electrical differences experienced in living systems are perceived by free nerve endings or receptors with sensory receptors. Whatever their physiological function, the common feature of receptors is that they are chiral. Thanks to this feature, excitatory molecules behave enantioselectively during binding.

Many pharmaceuticals and chemical compounds used in disease treatment are composed of chiral enantiomers with the same physical and chemical properties in racemic structure. In the pharmaceutical industry, one of the enantiomers is desired curative, therapeutic, etc. While the other enantiomer may be inactive, it may have a beneficial effect or may cause harmful side effects. Since there is a need for chiral compounds of enantiomeric purity in the pharmaceutical industry, it is important to develop appropriate separation methods and establish new strategies in the purification processes of chiral molecules from racemic mixtures. Many optical resolution methods are used to separate racemic compounds. However, classical methods require a long process. This situation creates high costs, and a low amount of optically active compound is obtained in return, therefore it is not preferred in the pharmaceutical industry. Membrane-based chiral separation processes are economical compared to other separation processes due to their high efficiency and energy saving. In addition, this method is preferred because the scale-up step is easy.

Chiral molecules

Enzymes: Enzymes, which are chiral compounds, play a role in the realization of many reactions with their cofactors and coenzymes. They act as biocatalysts. Enzymes, with their enantioselectivity, are catalysts for asymmetric synthesis in oxidation-reduction reactions.

Amino acids: The functions of proteins depend on their interactions with other molecules through chiral structures. Homochirality of amino acids is necessary for the gene to specifically code for protein because L- and D-amino acids form three-dimensional protein structures. For example, the amino acids alanine and serine each have a stereogenic centre marked with an asterisk (*). In nature, they occur as natural enantiomers. Proteins, on the other hand, are actually a single enantiomer, despite having many chiral centres.

protein, stereojenik merkez, kiral karbon
– A protein molecule and its stereogenic centres (red structures).

DNA: One of the basic building blocks of living things, the double-stranded DNA, in which genetic information is found, is also a chiral molecule. For example, the nucleic acid cytosine in DNA has three stereogenic centres indicated by an asterisk, and one can speak of chirality. Like proteins, DNA is a single enantiomer despite having many stereogenic centres.

DNA, stereojenik merkez
– Cytosine molecule (far left) and DNA strands marked with three stereogenic central star symbols, which are chiral molecules.

Carbohydrates: They are examined in three subgroups monosaccharides, disaccharides, and oligosaccharides. Carbohydrates are also in the class of chiral molecules.

gliseraldehit, stereojenik merkez
– Stereogenic centres of D- and L-glyceraldehyde, one of the simplest monosaccharides, are indicated by *.

Lipids: Lipids are chiral molecules, which are the most important units of the cell membrane. He earned this title thanks to his optical activity. The enantiospecific interactions involved here change the properties of the cell, which can significantly affect the role of membrane-bound proteins.

– Some chiral lipid molecules in the cell membrane.

Pharmaceuticals: The importance of chirality in the pharmaceutical industry is an undeniable fact. The enantiomer, which is a mirror image of each other, behaves as two different compounds in the chiral environment, in addition to the difference between the directions of rotation of the vibrational plane of the polarized light. Therefore, their chemical properties in the chiral environment are also different. Since enantiomers have chiral properties in living organisms and structures, they can act in two different ways on these living organisms and structures. In other words, enantiomers can have opposite effects on each other. For example, (S)-(-)-propranolol has been described as a β-blocker in the treatment of heart disease, but its enantiomer (R)-(+)-propranolol acts as a contraceptive. Therefore, the enantiomeric purity of this compound is very important in clinical use. The concept of chirality is very common in pharmaceuticals. Pravastatin sodium for cardiovascular diseases, sertraline hydrochloride for central nervous system diseases, salmeterol for respiratory system diseases, clopidogrel bisulfate for haematology diseases, esomeprazole magnesium for digestive system diseases, potassium clavulanate as an antibiotic can be given as examples.

While 56% of the drugs used by the patients are chiral molecules, 88% are found as racemic mixtures. However, when using racemic drugs, it is necessary to use two layers of the racemic mixture in order to fully absorb the unit amount of active substance. For example, (R,R)-chloramphenicol shows antibacterial properties, while (S,S)- chloramphenicol shows inactive properties. Therefore, using racemic mixtures is uneconomical as it wastes half of the resources. Therefore, a single enantiomer always shows more biological activity than a racemic mixture.

kloramfenikol, enantiomer
– Two enantiomers of chloramphenicol.

As a result, chiral molecules are of great importance for living things. After the discovery of the concept of chirality, studies on naming them were made easier in the expression of these molecules and the understanding of the structure of chiral molecules was facilitated. The right or left orientation of chiral molecules is the factor that changes the way it acts. This is due to the fact that the two enantiomers act differently from each other. Contributing to the formation of the basic building blocks of living things is one of the most important effects of chirality. The contribution of chirality to the pharmaceutical industry is great. Almost half of the drugs on the market are chiral and approximately 50% of them are enantiomer mixtures. From the past to the present, many chiral drugs have been produced, and while most of them have been beneficial, some have been harmed. Chirality is a concept that provides convenience in the field of drug production, if a solution is found for these damages and if the harmful enantiomers can be prevented from showing side effects in the living thing. Biological compatibility, metabolism rate, metabolites, secretion, potency and receptor selectivity, transporters and enzymes, and toxicity of the two enantiomers of chiral drugs can be different. The use of single enantiomer drugs can potentially lead to easier pharmacokinetics and more selective pharmacological profiles, despite reduced drug interactions and different metabolism rates of different enantiomers. Single isomer chemicals can be preferred to racemic chemicals because they are more effective, use less quantity and are more economical in terms of the production process.


This article is a part of the homework written by İremgül Çelikyurt and Melis Tarkan, our Organic Chemistry students for the Fall Semester of the 2020-2021 Academic Year.


References

  • Alija K. 2016. Biyolojik Aktif Bileşiklerde Kiralitenin Önemi. Lisans Araştırma Projesi. T.C. Ankara Üniversitesi Eczacılık Fakültesi, Farmasötik Kimya Anabilim Dalı.
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Our article entitled “Biochemical Significance of Biomaterials Based on the Chitin-Chitosan Axis”, which I wrote with my undergraduate students, has been published…

Our review article entitled “Biochemical Significance of Biomaterials Based on the Chitin-Chitosan Axis”, co-authored with my 2nd-year students Tamar Faraj and Mariam Ajam from NEU Faculty of Veterinary Medicine, was published in the journal “Acta Scientific Gastrointestinal Disorders (ISSN: 2582-1091)”.

I would also like to thank Ahmet Özer Şehirli PhD Assoc. Prof., Sevgi Gençosman DVM and Deniz Ceylanlı DVM, who contributed to the planning, literature review, writing, review and finalization of the article and with whom I enjoyed working and producing.

In our study, we conveyed the biological properties of the biomaterial called Chitosan, which is obtained from the polysaccharide called Chitin, which is the most common in nature and an important component of the exoskeletons of arthropods, and current approaches regarding its use in the field of health and my views in this direction from a biochemical point of view.

Click to access the article.

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