You Are What You Eat Biology Essay

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To begin with I would like to say that, drugs are not the natural products but are produced in nature and are identified as leads by biological assays and thus are the source of drug development. Although use of natural products in drug discovery has been decrease in last few years, 60 percent of anticancer and anti-infective drugs are obtained from nature. In past, natural compounds innovated new therapies which essentially contributed to understanding and identification of in vivo and in vitro biochemical pathways. Example: Phosphinothricin- the gene for N-acetyltransferase was transferred to plants to generate genetically modified crops. In ancient years, drugs were isolated from plants or animals products or sometimes from inorganic salts. Without nature it is not feasible to discover drugs though biologists and chemists have latest knowledge of biological systems and technologies as it is time-consuming, costly, tedious and difficult. The main sources of drugs are plants, microbial metabolites (Penicillin by Penicillium) and marine invertebrates (Ziconotide to treat neuropathic pain). Drugs are developed from terrestrial and marine dioactive substances extracted from plants, microbes and animals. Currently the stratergies to develop drugs is in rapid growth in both pharmaceutical and agrochemical industries. It has been found that human consumed drugs are mainly derived from plants. In current era, there are three major sources of new drugs: (a) original natural products (b) drugs derived semi-synthetically from natural products and (c) connectional synthetic compounds based on natural products. The new chemical entities used in production of drugs are natural products without modification; natural products with modifications, plant derived natural products, synthetic products, synthetic but natural product mimic and vaccines [1].

Discussion:

Microbe-animal interactions

There is a profitable relation between microbes and animals as it involves exchange of nutrients and maintenance of favourable habitat. This benefits animals to digest components like cellulose which is not easily digestible. Symbionts found in intestine can be beneficial to animal by producing vitamins and providing protection against pathogenic organisms or can be commensals. Entozoan algae provide nutrition to animals as they are photosynthetic. Endosymbiotic bacteria supplies light to aquatic invertebrates and fish.

Alkaloids derived from poison frog derivatives and their skin secretions

The first drug isolated from from poison frog is Epibatidine. In the pharmacology test performed it was found that mouse when they were injected with the drug epibatidine curved its tail over its back. This drug was later recognized as an anodyne. Thus this drug became more important in studying role of nicotinic receptors. Batrachotoxin drug was isolated from poison drat frogs and it was found that it was responsible for activation of sodium channels. The below diaram shows different types of alkaloids derived from poisonous frogs especially those belonging to Dendrobatidae family.

Fig1: The alkaloids derived from Dendrobatidae family [2]

Frog skin secretions: Many compound found in secretion of grandular gland plays a defensive role such as cardiotoxic, myotoxic, neurotoxic, vasoconstrictive, hypotensive and hallucinogenic effects. Dendrobatid frog has a typical chemical structure and is useful in studying cell receptor sites and in ion transport channels in cell membranes. Dermorphin, a peculiar opioid hepatapeptide drug produced in skin of leaf frogs plays a defensive role against predator which causes soporific effect and also plays an important role in pain relief mechanism to cope up with injury caused by predators. Their coping capability is due to (i) high occurrence of healed broken limb bones, (ii) Exhibition of loss of digits, parts of limbs [3]. As the skin is well supplied with blood vessels it can produce pain-killing substances which can be transported to the site of injury and thus help amphibians to keep on living during healing phase. The secretion of skin glands of toads also contains adrenaline, non-adrenaline and dopamines which can be used to distinguish evolutionary ancestry. Skin secretions of dried toad are useful in herbal medicines [4]. The drugs derived from frog skin secretions are used against skin and respiratory infections.

Pumiliotoxins in formicine ant

Pumiliotoxins [5]

There are eighty different alkaloids which are found in ants. These are pumiliotoxins, alloppumiliotoxins and homopumiliotoxins [6]. Pumiliotoxins contains alkaloids which are lipophilic. As mites are eaten by various poison frogs they are considered as main dietary sources of alkaloids in poisonous frogs. Pumiliotoxins found in formicine ants are emerged from more than one taxon of dietary arthropods [9]. It is less toxic than their batrachotoxin counterparts [7].

Birds harbour toxic alkaloids

Homobactrachitoxin, a neurotoxic drug is present in high concentrations in feathers of birds mainly feathers of belly, breast and legs which attaches to Na+ channels and then depolarizes electrogenic membranes. This drug is mainly found in Ifrita kowaldi and it kills lice and other parasites [8]. As batrachotoxins are non-volatile it can be inhaled via air when feathers carrying this toxic slough off.

Antiviral proteins from natural product extracts

Cyanovirin:

It is obtained from cyanobacterium Nostoc ellipososporum. It is a 101 amino acids protein with two tandom repeats each of 50 amino acids. It shows pseudo-symmetry and consists of two domains, each having independent glycan binding sites [9, 10]. This protein acts as an entry inhibitor for Human Immunodeficiency Virus [11].

Griffithsin

This antiviral protein is produced by Griffithsia sp. It terminates cell-cell fusion and also transmission of HIV infection by blocking CD4 binding receptors and attachment to viral coat glycoprotein. Thus it was found that this protein binds to glycoprotein in a monosaccharide-dependent manner. It can act as a protective compound against HIV and AIDS. It was produced in Nicotina benthamiana by introducing synthetic cDNA into TMV vector. N.benthamiana seedlings were then inoculated with infectious RNA transcripts in vitro and then the rTMV inoculums was purified. The major contaminant is TMV coat protein which is removed by filteration [12]. The in vivo efficacy of griffithsin was compared with Ebola Zaire virus in mice to see the percentage of survival and change in weight of mice. Moreover, it was found that all surviving mice had permanent neutralizing immunity against Ebola Zaire virus.

Bacterial histone deacetylase inhibitor

This compound inhibits activity of histone deacetylase. It is used in psychiatry and neurology as moods stabilizers and anti-epileptics. It is even used to understand various neurodegenerative diseases. The function of memory cells in mice can be increased by histone deacetylase inhibitor sodium butyrate or by knocking down HDAC2 gene in mice. It is also used in treatment of cancer. SAHA, Trichostatin- A, A-Picidin, Trapoxin-A, Azumamide-A, FK-228, Spiruchostatin-A and L-Argazole are different types of HDAC inhibitors.

Conclusion:

In conclusion I would like to say that with the use of HTS in pharmaceutical companies and due restriction of government on approval of drug in future the number of drugs derived from natural products will become next to zero. Due to sequencing of genome and use of single-molecule-real-time technique [13] it will enable to use metagenomics to produce drugs. It will also reveal silent pathways in plants which will help in production of new products and biocatalysts [14]. These drugs are used to treat cancer, neurological diseases, infectious disease, cardiovascular disease, disease related to metabolism, immunological, inflammatory and related diseases and even to treat genetic disorders. Moreover, due to launching of new drugs into market currently there are large ranges of drugs obtained from ‘Mother Nature’ which are undergoing clinical trials. More research on these compounds is going on as it is necessary for the augmentation of human health. In few years, the natural sources will become main components for novel drugs with improvement in pharmacokinetics and toxicology. The discovery of drugs by multidisciplinary approach which involves generation of molecular diversity from natural sources along with total and combinatorial synthetic methodology will provide good solution to the current crisis of drug production. Current improvement in isolation and structure determining technologies has reduced the problem of screening mixtures of complex molecules. Efforts to bloster the effect of natural chemistry diversity follow two main paths: (i) To simplify crude mixtures and to increase the impact of minor components in assays by creating natural product libraries. (ii) To use combinatorial synthesis to amplify the structural context in which the unique features of natural products are expressed. The assemblage of these technologies with advancement in genomics, metabolic engineering and chemical synthesis will exploit the use of nature’s small molecules in the search of new drugs.

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