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CHITIN

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Botulinum Toxin: Publications

Introduction

Chitin is the second most abundant polysaccharide (carbohydrate polymer) after cellulose, and is found widely distributed in nature as ordered macrofibrils (Zohuri, 2012). Chitin is a chief component of the invertebrate exoskeleton, wherein its main role is to provide strength. It is also found in fungal cell walls and bacteria. However, in industry, the main natural source of chitin is crab and shrimp cells, which are available in abundance from food catering. Therefore, large quantities of this polysaccharide can be obtained industrially for subsequent commercial use in the biomedical, photography, textile, paper, and pharmaceutical industries as a chelating agent which is both non-toxic and biodegradable (Reddy & Yang, 2015; Elieh-Ali-Komi & Hamblin, 2016). Although no vertebrate animal can degrade chitin, animals which consume insects often host symbiotic bacteria in their gut that are capable of digesting polymeric chitin into small carbohydrate molecules.

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Chemical, Physical and Biological Function of Chitin:

Chitin is the second most naturally abundant nitrogen-containing polysaccharide on earth (Dutta et al., 2004). A polysaccharide is a natural ubiquitous polymer whose molecules consist of simple sugars (monosaccharides/monomers) bonded together by specific types of covalent bonds known as glycosidic linkages (Udayan et al., 2017). 

 

The modified polysaccharide is composed of 2-(acetylamino)-2-deoxy-D-glucose (N-acetyl-D-glucosamine) units which form β-(1→4)-linkages, similarly to those formed between glucose subunits in cellulose (Dutta et al., 2002). Although it is not found in cellulose-containing organisms, chitin is often viewed as a cellulose derivative as a result of its structural similarity with cellulose. Chitin is in fact structurally identical to cellulose with the exception of an acetyl amine group (-NHCOCH3) replacing one hydroxyl group at the C-2 position of each monomer (Hudson & Smith, 1998). This modification allows for increased hydrogen bonding between neighbouring monomers, giving rise to a stronger, resilient chitin-polymer matrix (Dutta et al., 2004).

 

Chitin is insoluble in water, however once deacylated a soluble chitin-derivative arises (Cheung et al., 2015). Chitosan is the primary derivative of chitin recognised as a linear polymer composed of haphazardly dispersed N-acetyl-D-glucosamine and β-linked D-glucosamine. Chitosan, similarly to chitin, has various chemical properties most notably its available reactive amino and hydroxyl groups as well as its ability to chelate numerous transitional metal ions (Dutta et al., 2004).















 

Figure 1: Chemical structure of Chitin and Chitosan. Originated from Nilsen-Nygaard et al., 2015. 

 

Physical

Chitin is a polysaccharide that is found naturally occurring within a multitude of different organisms such as arthropods and fungi (Younes & Rinaudo, 2015). It is a colourless (Younes & Rinaudo, 2015), minimally toxic substance, that is not soluble in the solvents commonly available and is not reactive within the mammalian gastrointestinal system (Rinaudo, 2006). Moreover, chitin is a biodegradable molecule since the enzyme which breaks it down, known as chitinase, is abundant in nature (Rinaudo, 2006). These organisms synthesise chitin for use within their cell walls or exoskeletons and within these structures, it is found in its native conformation as organised, crystal-like microfibrils (Younes & Rinaudo, 2015). 

Chitin exists in two different polymorphic states (Tsurkan et al, 2021), which are known as allomorphs, and these are the α form and the β form (Younes & Rinaudo, 2015; Rinaudo, 2006). In both forms, the chains of chitin are considered to be arranged in sheets that are strongly adhered to each other by multiple intra-sheet hydrogen bonds however the difference between the two forms is that in the α form, inter-sheet hydrogen bonds are also present which are produced by the hydroxylmethyl groups that are present in the chains (Younes & Rinaudo, 2015; Rinaudo, 2006). Moreover, the α form has been determined to be the more naturally occurring form, as the β form occurs less in nature (Younes & Rinaudo, 2015). There was also the description of a third allomorph of chitin, known as the γ form, however there is still considerable debate on whether this is a separate form of chitin or part of one of the other forms (Rinaudo, 2006; Tsurkan et al, 2021).       

Within the organisms that synthesise chitin as well as generally in nature, chitin is not found completely on its own in a pure state (Tsurkan et al, 2021). In fact, this polysaccharide is able to form strong bonds with a variety of different molecules such as proteins, biominerals like calcium carbonate, lipids, polysaccharides and pigments and due to this reason, within nature, chitin arranges itself with these molecules on a nano scale to form chitin-pigments, chitin-mineral composite biomaterials and chitin-proteins (Tsurkan et al, 2021). The ability of chitin to form these latter structures as well as its inherent insolubility in most solvents has made the identification of chitin (Tsurkan et al, 2021), as well as the elucidation of its physical properties quite challenging and thus, certain information pertaining to its physical properties is still limited (Rinaudo, 2006). 

Biological

Chitin is a large structural polysaccharide found in many different species such as invertebrates, fish, fungi cell walls, and insects. It can be considered to be the second most abundant substance within the biosphere, cellulose being the first. 

This carbohydrate was first identified in Fungi by Henri Braconnot in 1811 where he named it ‘fungine’, whilst another scientist Auguste Odier isolated the compound from beetle cuticle and named it ‘chitine’ derived from Greek meaning ‘covering’. 

 

The biological function of chitin changes according to the organism it is found in. For instance, in soft-bodied organisms, it is produced as a mechanical support. Insects and arthropods utilise chitin as a component of their exoskeleton, as well as being present within the body wall, gut lining and mouth parts of insects. Whereas in chitinous fungi, chitin is used as a replacement for cellulose within their cell wall. Due to the presence of this molecule within so many insect structures and fungi, chitin degrading enzymes can be used within certain fungicides and insecticides to eradicate pests. 

 

Chitin has many applications whether in the medical industry or not, due to its non-toxicity, biodegradability, and antimicrobial properties. An example of the use of this material in the medical field is for the use of surgical stitches, which degrade/dissolve over time, thus not requiring the removal process.

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Applications of chitin and its derivatives in medicine:

Although chitin is a relatively simple and common molecule, recent studies have found that it has several applications in medicine. One of these is the use of chitin in anti-inflammatory medication for diseases such as colitis, hepatitis, gastritis and periodontal disease. This is an ideal replacement to the typical non-steroidal anti-inflammatory drugs which are known to cause several side effects such as problems in the kidneys and liver as well as addiction (Park & Kim, 2010).

Silva et al. (2009) discovered that by degrading chitin into its derivative chitosan, it is able to inhibit tumour necrosis factor (TNF) and interleukin-8 from mast cells, both of which are involved in the activation of inflammatory responses in the body.

Apart from this chitin oligosaccharides (COS) are also involved in tumour inhibition through the activation of lymphocyte cytokines which increase T-cell proliferation (Park & Kim, 2010).  Quan et al. (2009) further explain that COS can act as inhibitors of heparinase which is involved in tumour invasion, metastasis and angiogenesis.

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Figure 2: Anti-tumorigenic activity of Chitooligosaccharides (COS)

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In addition, chitosan also has applications in drug delivery as it can help increase absorption of the drug as well as stabilise the drug components which helps increase drug targeting. Furthermore, chitin and chitosan derivatives can be conjugated with certain types of anticancer agents in cancer treatment. This has been found to reduce therapy side effects as well as allow for the slow, gradual release of the drug in cancer tissues which increases the effectiveness (Park & Kim, 2010).

Possible Role of Chitin the Pathology of Alzheimer’s Disease

Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterised by progressive memory loss combined with cognitive and behavioural impairment. AD afflicts an estimated 44 million people worldwide and has been identified as the primary cause of dementia, contributing to 60-70% of all cases.

AD is characterised by two neuropathological hallmarks: the deposition of extracellular amyloid β peptide (Aβ) and the formation of intracellular neurofibrillary tangles (NFTs) comprised of abnormally hyperphosphorylated tau, a microtubule-associated protein. However, it was only until recently that scientists discovered that the extracellular amyloid plaques observed in AD contain chitin. In a clinical study, it was found that chitin levels are elevated in the central nervous system, but cerebrospinal fluid and plasma of AD patients. Whilst chitin is tolerated within much of the body, it could be particularly toxic to neurons within the brain (neurotoxic). Chitin could potentially accumulate in the brain over years eventually triggering the cognitive decline characteristic in AD pathology. This hypothesis is strengthened by cell culture studies which demonstrate that neuronal cell lines incubated with GlcNAc, the sugar that constitutes chitin, undergo high rates of cell death.

Conclusion

The use of chitin derivatives, such as chitosan, to produce biodegradable plastic has been an active area of research for the past few years (Zohuri, 2012). Additionally, major efforts are being made to use chitin as a polymer scaffold in studies investigating wound healing and tissue growth, as well as in the manufacture of surgical thread and bandages. Problems with lack of elasticity, however, currently hamper further wound dressing development. Instead, recent studies have been looking into the potential use of chitin in robust building tools and structures made of a concrete-like composite material.

The potential application of chitin in drug and vaccine delivery is also under increasing investigation (Elieh-Ali-Komi & Hamblin, 2016). 

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References:

 

Castellani, R. J., Perry, G., & Smith, M. A. (2007). The role of novel chitin-like

polysaccharides in Alzheimer disease. Neurotoxicity research, 12(4), 269-274.

 

Cheung, R. C. F., Ng, T. B., Wong, J. H., & Chan, W. Y. (2015). Chitosan: an update on potential biomedical and pharmaceutical applications. Marine drugs, 13(8), 5156-5186.

 

Chitin and Chitosan – Nutrients Review. (2015, August 17). Retrieved from www.nutrientsreview.com/carbs/insoluble-fiber-chitin-chitosan.html

Chu, D., & Liu, F. (2018). Pathological changes of tau related to Alzheimer’s disease. ACS chemical neuroscience, 10(2), 931-944.

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Da Silva, C. A., Chalouni, C., Williams, A., Hartl, D., Lee, C. G., & Elias, J. A. (2009). Chitin Is a Size-Dependent Regulator of Macrophage TNF and IL-10 Production. The Journal of Immunology (1950), 182(6), 3573-3582. https://10.4049/jimmunol.0802113

 

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Elieh-Ali-Komi, D., & Hamblin, M. R. (2016). Chitin and Chitosan: Production and Application of Versatile Biomedical Nanomaterials. International Journal of Advanced Research, 4(3), 411-427. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094803/

 

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Tsurkan, M. V., Voronkina, A., Khrunyk, Y., Wysokowski, M., Petrenko, I., & Ehrlich, H. (2021). Progress in chitin analytics. Carbohydrate Polymers, 252, 117204. 10.1016/j.carbpol.2020.117204

 

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Zohuri, G. (2012). Polymer science: a comprehensive reference.

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