"When you get down to looking at biology at the molecular level - understanding the fundamental processes of life - it's all chemistry", Professor David Garner said, who is the president of the Royal Society of Chemistry. He made this comment after some chemists disagreed with the 2009 chemistry Nobel Prize, which was awarded to Venkatraman Ramakrishnan, Thomas Steitz and Ada Yonath who did their studies in the structure and function of the ribosomes. Indeed, if we look closer at our bodies into molecular level, we are all constructed by chemical molecules; also we are surrounded by chemistry, such as oxygen, nitrogen, water molecules. Furthermore, chemistry plays a very important role in improving our lives as well, for example, the medicines used to cure many diseases are all organic compounds. Simultaneously, the knowledge known about the life can also be applied in chemistry research. It can be easily seen that there is a very strong link between lives and chemistry.
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The aim of this essay is to discuss about the life in chemistry level, the importance of chemistry to our lives and how we improve chemistry using the information obtained from the world of life. Finally, one of main societal problems related to chemistry and life will be discussed and how chemists are trying to change current status will also be explained.
The relationship between chemistry and life
As one of science subjects, chemistry has been developed for thousands of years since it was firstly used to make cosmetic powder by ancient Egyptians. The understanding in chemistry has changed over time and in different area of the world, but it is always developing and improving. The knowledge of chemistry was developed at the similar time when science was explored. Since the beginning of the nineteenth century, chemistry has taken a place in the centre of science, playing an important role in connecting physics and biology.
There are many different branches in chemistry, such as organic chemistry, inorganic chemistry, physical chemistry, biochemistry, etc. Each of them is tightly bound to life in different aspects. For example, most chemical compounds in living species are carbon-containing hence belong to the branch of organic chemistry, while transition metals like Fe, Pt are commonly involved in many enzymes which are related to inorganic chemistry. Biochemistry is a branch which investigates chemical reactions in biological setting, whereas physical chemistry is more related to the kinetic and thermodynamic properties of these reactions. The relationship between chemistry and life can be generally divided into three following catalogues: chemistry of life, chemistry for life and chemistry from life.
Chemistry of Life:
There are many facts showing that chemistry spreads out in living bodies, including both animals and plants. There are 25 different elements which are essential for life, four of which, C, O, H and N comprise 96 % of the total, and the other 21 make up the remaining 4%. A special group of elements called trace elements are of particular importance in animals although only minute quantities are present. For example, cobalt is coordinated to a corrin ring system in the vitamin B12, and iodine has been proven to be essential in the thyroid hormone. In addition, many metal elements, such as iron, zinc, copper, manganese and molybdenum, are significantly invovled in catalytic enzymes in animals .
The elements are "assembled" together, producing chemical molecules around living bodies, and the simplest and most abundant one is water (H2O), which comprises up to 60% of the whole weight in human body. More complicated bioorganic compounds present in living systems are carbon-containing, and they can be generally grouped into following classes, carbohydrates, lipids, proteins and nucleic acids, which are vital for life. These biochemical compounds interact with each other in the living cells under the catalysis of special groups of proteins, enzymes, to produce energy and building blocks required for normal cell function. Here will discuss an example of one particular biochemical process, fatty acid degradation, to demonstrate the chemistry that is involved in this energy generating process.
Fatty acid degradation is a process in which fatty acids are broken down to small molecules known as acetyl CoA. The molecules then can enter into citric acid cycle to produce the energy currency of the body, Adenosine triphosphate (ATP). The chemical reactions involving in the breaking down of fatty acid molecules will now be introduced from the perspective of chemistry. Initially in this process, the fatty acid will be activated by Coenzyme A (CoA) to form its CoA ester, acyl CoA, which then will be transported into mitochondrial matrix by using carnitine. The general scheme is shown in Figure 1.
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After entering mitochondria matrix, acyl CoA starts to be metabolised in a 4-step sequence of chemical reactions, which are comprised by oxidation, hydration, oxidation and thiolysis, as shown in Figure 2. The first step is the oxidation from alkane to alkene using flavin adenine dinucleotide (FAD) as oxidation agent, which is a good electron acceptor and takes 2 protons and 2 electrons away from acyl CoA. Similar oxidation process is carried out in the third step to oxidise an alcohol to a ketone with the use of NAD+. As another common electron acceptor in biochemical environment, NAD+ is operated in a slightly different manner, as shown in Figure 3.
The second step of fatty acid degradation which adds a water molecule across a double bond of an alkene is defined as hydration. Hydration usually occurs in acidic aqueous condition in chemistry laboratory. It also works in physiological environment, but the process needs to be facilitated by enzymes, which is enoyl CoA hydratase in this circumstance.
The last step is known as thiolysis and it is catalysed by thiolase. One more molecule of coenzyme A is required to complete this biochemical reaction. The extra molecule of CoA cleaves the carbon chain between two carbonyl groups in 3-Ketoacyl CoA, which is produced in the third step. The resulting products are acyl CoA shortened by two carbons and acetyl CoA, and latter of which will be utilised in the production of ATP in citric acid cycle. The citric acid cycle is one of the most critical biochemical pathways generating energy, but its details will not be discussed in this essay due to the limitation on scope.
By revealing the biochemical transformation involved in the ?-oxidation pathway of fatty acids metabolism and highlighting some of the chemistry involved in, it has been shown that our lives are full of chemistry reactions, even only in one single biological process. Like catalysts used in accelerating reactions in the chemistry laboratory, there are also a group of natural biological catalysts, which are known as enzymes and very common in life.
Chemistry for Life:
With the progress in understanding the chemistry of life as well as theoretical chemistry itself, scientists started to combine both together. This has enabled chemists to look at how to improve our lives by applying their theory into practice. Especially after the double-helix model of DNA structure was discovered by Watson and Crick in 1953, the application of chemistry in human body has been extensively studied. One of the most important research areas where chemists are trying to improve the quality of life is in pharmaceuticals. This is where scientists pursue the causes of diseases and look for cures in the form of drugs, which are normally organic molecules designed and synthesized by chemists during drug discovery process. The following example will explore aspirin to show what they have achieved in the research and how our lives benefit from chemistry.
As stated in Chemistry of Life section, enzymes play essential roles in biochemical environment since most biochemical reactions are catalysed by enzymes. However, every coin has two sides, enzymes are also, sometimes, the origin of diseases in some circumstances. For example, Also, problems will arise if a specific type of enzyme is catalysing an unwanted reaction, producing the compound that is harmful to living organisms. Prostaglandin synthase, a key enzyme in the synthesis of prostaglandin, is an example of the latter case. Prostaglandin (PG) is released in damaged cells and causes headache and vascular pain in human, therefore, to relieve the pain and inflammation caused, it is useful to decrease the amount of prostaglandin present in the body by inhibiting the enzyme prostaglandin synthase.
Aspirin was discovered by Felix Hoffmann, a German chemist, in the end of 19th century, and its synthesis is shown in Figure 5. The synthesis is straightforward and SN2 mechanism is applied. Phenol group in salicylic acid acts as nucleophile which attacks the carbonyl in acetic anhydride in acidic condition. This results in the elimination of acetic acid and the formation of the desired product, aspirin.
The function of aspirin, characterised as a type of irreversible enzyme inhibitor, is to bind the enzyme prostaglandin synthase irreversibly, preventing the formation of PGs. The detailed hypothetical mechanism is shown in Figure 6.
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Aspirin molecule comes into the active site of PG synthase, forming hydrogen bonds with the phenol of peptide Tyr-385 residue and hydroxyl group of peptide Ser-530. Ser-530 of PG synthase is acetylated by aspirin, while Tyr-385 is guiding aspirin to the right position allowing it to approach Ser-530. As a result, after Ser-530 being acetylated, PG synthase is inactivated and loses the ability to catalyse the formation of PG. Furthermore, the ache is eased due to less stimulation of nerve endings and also the body temperature is stable. The desirable pain reducing effect of aspirin has made it one of the most widely used drugs in the world.
There are also many other examples showing the chemistry involved in life. For example, in the aspect of agrochemistry, the absolute configuration of chiral agrochemicals is of particular importance in their biological activities. This point is emphasised by analysing the development of a herbicide that was developed ten years ago. Metolachlor, one of the most important herbicides of its time, has two enantiomers, (S) and (R), as shown in Figure 7. (S) enantiomer is active, whereas (R) is completely inactive. Before 1997, the synthetic methods available to chemists only enabled the racemic mixture to be synthesized, which means half of the material was effective waste. However, in 1995, enantiopure (S) material was synthesized by using asymmetrical hydrogenation and a lot of money was saved consequently. This is another example showing how important chemistry is in daily life, and the details of the asymmetric synthesis involved will not be revealed here.
Chemistry from Life:
After discussing how chemists apply their knowledge in lives, now it is the time to take "compensation" from our lives into chemical research. The Human body can be considered as a big reaction "pot" within thousands of different reactions carrying on simultaneously, most of which are under the catalysis of enzymes. Except from catalysing chemical reactions with a much higher efficiency than normal catalysts, enzymes also have some other significant advantages: firstly, only relatively mild conditions (physiological conditions) are required for them to work; secondly, the enzymes are highly chemoselective, stereoselective and enantioselective. Therefore, enzymes isolated from living organisms or "hand-made" could potentially be used in chemistry research in either academic or industrial environments. In fact, chemists had already started to explore the use of enzymes in many chemical reactions in the early nineteenth century. An example of one particular enzyme, aldolase, will be introduced here.
The most useful method of synthesising carbon-carbon bond is considered to be by aldol condensation. When an aldehyde or ketone is reacted with substituted enolates, diastereoisomers are formed due to more than one stereogenic centre hence the reaction becomes limited when only one diasteroisomer is required. However, this issue can be addressed by using an enzyme named aldolase. There are two types of aldolases existing that chemists can employ, and these have slightly different mechanism. The generalised mechanisms are shown in Figure 8.
In Pathway a, ketone reacts with the active site, lysine residue in type I aldolase, forming enamine which then attacks the aldehyde. In type II, the ketone is reacting with histidine residue of the aldolase instead of lysine, and also Zn2+ is involved as co-factor. Due to the binding between aldolase and the ketone, the freedom of attacking towards the aldehyde is highly restricted sterically, resulting in only one diasteromer as the final product
Previous chapters have discussed the chemistry involved in life, how chemistry can be applied in our life and how life can return the favour and help chemical research. A brief overview of these has been provided. It can be seen that a good relationship between bench science and nature has been set up, and each of them is benefiting from the other. However, there are more and more challenges coming out with the development of the society, awaiting chemists to tackle. One of most critical problems is Acquired immune deficiency syndrome (AIDS), and this disease is now at pandemic levels and an alarming rate of increased infections. The data in Figure 9 is provided by UNAIDS-WHO Report, showing the estimated number of people living with HIV globally from 1990 to 2007.
AIDS is related with a virus known as Human immunodeficiency virus (HIV), which is a retrovirus containing deoxyribonucleic acid (RNA) and reverse transcriptase. HIV invades lymphocytes cells (CD4+) in human immune system and takes over the cells reproductive machinery to produce copies of itself. This is initiated by the production of DNA by reverse transcript process and then viral protein by translation using another unique protease: HIV protease. As a result, the number of CD4+ will be reduced significantly after being attacked by HIV. Eventually, the immune system of patients is compromised and they lose all of their immunity and die
Currently, there are some drugs available which inhibit either reverse transcriptase or HIV protease, for example, AZT, 3TC and Crixivan as shown in Figure 10. However, HIV mutates and becomes resistant to the drugs, which means a combination of different drugs will be needed and consequently the cost will increase. The financial problem becomes even more serious in poor areas, where people cannot afford medical tests and transport costs needed to go to clinics.
Therefore, to remove the continuous threat of AIDS to human beings and control the epidemic, the most effective and long-term solution is an HIV vaccine, which can protect humans from being affected and prevent the transmission of the virus. A few trials have been attempted in the past, but none of them succeeded so far due to the diversity of HIV that could potentially limit the value of any vaccine candidate. Furthermore, some basic information regarding to AIDS are still not completely known as well as how the host cells invaded respond to HIV. All these make it extremely difficult to design a successful vaccine using the same way of making other vaccinesand require chemists as well as biochemists to work harder in their areas in both academic and industrial environment and develop more potent drugs or vaccines, in the hope of making a breakthrough in treating this terrifying disease in the near future.
To summarize, there is a significant link between chemistry and life. Firstly, chemistry exists in every living species, and the presence of chemistry has provided the fundamental needs for life, such as energy and nutrition. Also, every small movement in the life is related to a chemical route, for instance the growth of plants and the food digestion of animals. Secondly, the chemistry knowledge gained in years of research can be utilized to improve health and quality of life, especially in the aspect of medicines. Without the drugs synthesized by chemists, humans would be suffering from many diseases which do not have effective cures for. Thirdly, chemists are simultaneously applying the chemistry occurring in life back to their research programme, helping them to solve the puzzles.
Unfortunately, there are still many problems regarding chemistry and life out there, for example, many serious diseases like AIDS, various cancers, are still threatening our health, and the solutions have not yet been found although chemists have been working on this area for many years. But chemistry is developing with time, so there is no eternal problem and chemists will be able to discover new ways of treating these diseases. Moreover, it is believed that the relationship between chemistry and life will become even stronger and closer in the future, and the importance of their collaboration will also be more notable once the chemistry of, for and from life are better understood. As a result, more and more unsolved problems start to be more accessible eventually.
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