Chemistry

DNA is a nucleic acid which is pervasive in nature and whose main function is to carry genetic information. As the hereditary material, it has certain distinctive physicochemical, topological, thermodynamic and electrical properties which enable it to perform this function with stunning accuracy. For instance, these properties enable the DNA molecule to remain stable, to replicate and to carry the billions of genes that code for proteins and determine the phenotype while at the same time being able to fit in the cell. This essay looks at the structure of the DNA in an in-depth manner. The various features of DNA are considered and correlations made with its biochemical role in the body.

The Primary, Secondary and Tertiary Structure of DNA
DNA is made up of 2 polynucleotide strands. These strands are not only anti-parallel but they are also complementary. The polynucleotide strands are composed of a sugar-phosphate backbone on the outside, and nucleotide bases on the inside. As such, the primary structure of DNA is made up of sequences of nucleotides. The nucleotide bases which flank the sugar-phosphate backbone are either purine or pyridine bases. The 4 basic bases include adenine (A), thymine (T), cytosine (C) and guanine (G). Adenine and guanine are known as the purines while cytosine and guanine are known as pyrimidines. The purines have 2 rings while the pyrimidines are made up of only 1 ring. The complementarity of the polynucleotide strands occurs because of the specificity of base pairing. Adenine pairs with thymine while cytosine pairs with guanine. However, non-conventional base pairing where adenine pairs with cytosine and guanine with adenine has been observed. This occurrence has been attributed to the wobble effect. In some instances, some DNA molecules have unique bases. DNA may be circular or linea.

Figure  SEQ Figure  ARABIC 1 Base pairing in DNA. A pairs with T and C pairs with G.
The 2 strands are held together by hydrogen bonds that form between the complimentary base pairs. Two H bonds reinforce the A-T pairs while 3 H bonds reinforce the G-C pairs. This is a very important feature with significant ramifications on the biochemical role of DNA. For one, the base composition determines the melting point of the DNA. Since the A-T pairing is fortified by only 2 H bonds, DNA which is rich in these 2 bases has a lower melting point. On the other hand, the G-C bonds are fortified by 3 H bonds therefore DNA that is rich in GC has a higher melting point. When DNA is subjected to temperatures above the melting point, the H bonds are broken and the 2 strands come apart. In other words, the double stranded DNA is converted into the single stranded form.

Figure  SEQ Figure  ARABIC 2 Diagram showing the secondary structure of DNA. The nucleotides are made up of the deoxyribose sugar, a purine or pyrimidine base and a phosphate group. The nucleotides are located inside the sugar-phosphate backbone. A pairs with T and G with C and the 2 polynucleotide strands are kept together by weak hydrogen bonds

When the temperature goes below the melting point, the H bonds between the complementary bases on the different strands are re-established and the double stranded form of DNA is reformed. In other words, the DNA re-anneals. This property also has an effect on the biochemical role of DNA as the two strands must be separated before replication or transcription can occur and proteins necessary for cellular functions to be produced. The relatively weak H bonds make it easy for enzymes known as helicases to unwind the DNA during replication and transcription and this enhances the efficiency of the 2 processes. DNA absorbs light at 260nm. When the DNA is denatured, the absorbance of light increases. The implication is that single stranded DNA has a higher absorbance than the double stranded form.
   
The sugar moiety in DNA is deoxyribose sugar. This is a pentose sugar with a H at the 2 position. In contrast, the other nucleic acid which is RNA has a hydroxyl (OH) group at the same position. The H group at the 2 position on the DNA molecule makes it to be more stable and this is important for the molecule to be able to carry out its biochemical roles.

The sugar and phosphate groups of adjoining nucleotides are connected with covalent phosphodiester bonds. These phosphodiester bonds are stronger than the H bonds between the different bases. The phosphate groups are negatively charged and this confers a net negative charge on the entire DNA molecule. As will be seen shortly, this is very important for DNA since it enables the DNA to be highly compacted so that it can fit into the cell without compromising its ability to carry lots of information through the billions of genes it carries. The net negative charge also has a significant effect on the behaviour of the DNA in solution. In solution, DNA can exist in 3 different forms. The most common form of DNA is B DNA (1, 2). The other forms of DNA which have been observed in solution are A DNA and Z DNA. The different forms of DNA will be considered shortly.

In terms of its secondary structure, DNA exists in a double helical form. The 2 polynucleotide strands wind about a common axis, creating a right-handed double helix. There are alternate grooves on the double helices and these are called the major and minor grooves. The major groove is 12 while the minor groove is 6. The major grove is also deeper than the minor groove. These grooves play an important role in many biochemical processes. For instance, the minor groove serves as an attachment site for DNase 1. The major groove is used as an attachment site by proteins which regulate the expression of genes. These regulatory proteins are defined by their structural motifs and include the helix-turn-helix, helix-loop-helix, leucine-zipper, steroid hormone, homeodomain and zinc finger motifs. They bind onto the major groove and control many cellular processes. As can be seen therefore, the unique chemical composition of the grooves enables proteins to be expressed in a precise manner as it confers sites for adherence of the regulatory proteins.

Different forms of DNA
As implied before, the commonest form of DNA is B DNA. This form of DNA consists of 10 base pairs per turn. Since each complete turn is 360, the rotation per base pair is 36. Generally, the B DNA is long and narrow in shape and has a diameter of 1.9 nm. The distance between the bases is 0.34nm. B DNA has no unique bases and occurs when there is plenty of water in the cell surroundings (92 water). B DNA spirals to form major and minor grooves and these groves are important for proper cellular function as DNA binding proteins attach to these grooves and help to regulate the expression of genes.

DNA can also exist as A DNA when there is less water in the surroundings (75 water). Even though A DNA has not been isolated under physiological conditions, it is a right handed helix with 11 base pairs per turn. Thus, the rotation per base pair is 32.7. The distance between the bases in A DNA is 0.26nm, the diameter is 2.3 nm and the overall shape is short and wide.
Z DNA is formed by alternating purine and pyrimidine bases. Unlike B and A DNA, Z DNA is a left handed helical structure with 12 base pairs per turn and a rotation of -30 per base pair. The distance between the base pairs is 0.37nm and the overall shape is elongated and narrow. This form of DNA also has only 1 deep groove. B DNA can interchange to the Z DNA if it is methylated at the 5 carbon or whenever negative supercoiling occurs.

In terms of its tertiary structure, DNA is supercoiled and preformed by higher chromatin folding. Supercoiling can either be negative or positive depending on whether the double helices have been underwound or overwound. B DNA usually manifests negative supercoiling and this is very important for proper cellular function since molecules that are negatively supercoiled can be easily unwound to enable replication and transcription to occur. Conversely, positively supercolied molecules are not easily unwound.

It was also mentioned before that the negative charge of the DNA is important for compaction. This is especially so in eukaryotes because DNA is wound around positively charged histone proteins which are rich in the basic amino acids and especially lysine. There are 5 types of histone proteins and these are H2A, H2B, H3, H4 and H1. Two units each of H2A, H2B, H3 and H4 associate to form a histone octamer onto which the DNA is wound. H1 stabilizes the formation. The linkage between DNA and the histones is very strong due to the attraction between the negative charges on the DNA and positive charges on the histones. Having been wound onto the histones, the DNA is further folded onto itself many times. This not only helps to compact the DNA and make it fit into the cell but also has significant ramifications on the expression of genes and consequently the production of proteins. It means that the strong bonds between the DNA and histones must be weakened so that the nucleotide bases are exposed for replication and transcription to occur and thereafter re-established after these processes are over. In a sense, it plays a vital role in biochemical processes as it prevents the constitutive replication and expression of genes and allows these to occur if and only if there is a need as indicated by specific mechanisms.

DNA exists as a double stranded helix and may either be right handed as in A and B DNA or left handed as in Z DNA. The helices are made up of a sugar-phosphate backbone on the outside and nucleotides on the inside. The nucleotides are made up of the deoxyribose sugar, a purine or pyrimidine base and a phosphate group. A pairs with T and G with C and the 2 polynucleotide strands are kept together by weak hydrogen bonds. Major and minor grooves innervate the helices and the molecule is negatively charged.  In conclusion, it can be stated that DNA is a highly complex molecule with several distinctive physicochemical, structural, thermodynamic and electrical features that are important for its role as a carrier of genetic information.

A.  To prevent leaking of hydrogen being prepared and to prevent any air entry in the   test tubes generating hydrogen, because H2 is highly flammable gas.
B. Zinc reacts with dilute Hydrochloric acid to form Zinc Chloride (Clow, 1952).
C.  In the experiment to generate oxygen, manganese is used as a catalyst to speed up the reaction under lower temperature.  Manganese does not change after the reaction. The most common compound of manganese used as a catalyst in oxygen generation experiments is MnO2. However, when pieces of Manganese are used in the reaction to generate Oxygen react with oxygen to form MnO2 (Kiefer, 2002).
D. 2H2  O2  2H2O.
E. Bromthymol blue is an indicator and therefore as a confirmatory test to for presence of carbon dioxide in the experiment,  where it changes to green and then yellow in the presence of CO2.
F. The solution may be assumed to be neutral when Bromothymol blue is a murky green

GasColorGlowing splintLimewater reactionBromthymol blue reactOxygenColorlessIn the presence of oxygen, the glowing splint is re-ignited or re-lighted.No observable changeIt turns from blue to yellow in colorHydrogenColorlessPop sound is produced when glowing splint is put in a container   containing hydrogen.No observable changeThe color of bromothymol blue turns from blue to yellow in the presence of hydrogen, this because the pH of hydrogen is on neutral scale.Carbon dioxideColorlessWhen put a glowing splint in a substance containing carbon dioxide it goes out.The clear lime water will turns into milky precipitate in the presence of carbon dioxide.Turns from blue  to green then yellow in the presence of  carbon dioxide

Oxygen, hydrogen, and carbon dioxide are colorless. Hydrogen burns a glowing splint by producing pop sound. Oxygen re-ignites the glowing, whereas carbon dioxide puts off the glowing splint since it does not support combustion. Hydrogen and oxygen show no observable change when mixed with lime water. However, carbon dioxide reacts with lime water (calcium bicarbonate) making lime water to turn from clear appearance to cloudy or milky precipitate. Therefore, lime water can be used to detect the presence of CO2 gas. Finally, bromothymol blue indicator turns from blue to yellow in color in the presence of oxygen and hydrogen. The indicator turns from blue to green and then yellow in the presence of CO2.

This project is a study of the chemical process involved in electrolysis and its specific application in electroplating. Electrolysis is the process by which electricity is transmitted through molten solution forms.  The chemical process involves the movement of mobile ions present in a solution which are attracted to either the positively charged anodes or the negatively charged cathodes (Masterton et al, 1985, p. 701). Electrolysis is made possible through the connection of the solution containing ions (electrolyte) to an external electrical circuit connected to a power source maintained at a certain potential difference. For instance, a dry cell maintained at a potential difference of 1.5v allows electrons to flow from the negatively charged terminal to the positively charged terminal. When these terminals are connected through connecting leads to electrodes, the electrons are able to flow freely. When dipped in an electrolyte, the potential difference between the two electrodes combined with electrostatic forces between ions present in a solution allows the free flow of electrons in such a manner that an electric circuit becomes complete. A simple electrolysis experimental set up is as shown below
Fig 1 an electrolysis experiment set up

Fig 1 Illustration of an electrolysis experiment set up. Adapted from httpwww.rustyiron.comengineselectrolysiselectrolysis.jpg
The anode is the electrode connected to the positive terminal of the power source while the cathode is connected to the negative terminal.
In conventional electrical flow, the actual flow of electrons starts from the negative terminal to the external circuit and back to the positive terminal. In this diagram, electrons flow from the negative terminal and enter the electrolyte through the cathode. The electrolyte contains  and  charges which either repel or attract the electrons. Since the anode is positively charged, the electrons and the negatively charged ions are discharged at the anode while the positively charged ions are discharged at the cathode. The movement of these ions is responsible for completing the circuit and therefore establishes the electrolyte as electrical conductors.
Industrial Application of Electrolysis in copper electroplating
Due to its close connection with electricity principles, electrolysis has a wide variety of applications. This study will analyze electroplating as one of the widespread industrial application of electrolysis. Chemical electroplating is the process by which a metal coating of higher quality is applied to a metallic object through an electrochemical process.  The main objective of commercial electroplating is to improve appearance of a metal surface, to achieve special surface properties or for metal protection (Osborne, 2009, p. 1). Copper is preferred in electroplating because it is cheap and has an alluring golden appearance. The metal also has a high efficiency in plating and many copper plated objects are well covered. In industrial plating, copper is buffed to improve its plating efficiency and improve its excellence as an undercoat in cases where subsequent plating is required. The process of electroplating utilizes the following principles in electrochemistry
The metal at the cathode normally dissolves during electrolysis.
Electrons from the cathode are attracted and deposited at the anode
The apparatus normally utilized in the electroplating process are a direct current source, lead connecting wires, electrodes (normally carbon or graphite), the object being electroplated, an electrolyte (incase of copper plating, copper sulfate solution is normally used) (Baron, J. et al, 2009).
Methodology
An electrolyte solution (copper sulfate solution) is prepared and poured in an industrial container (beaker in a laboratory context)
Electrodes are connected to an external supply of a direct current and dipped into the electrolyte (pure copper is used as the cathode).
The metal to be plated is connected at the anode and dipped in the solution too. It would also be appropriate to use the object to be plated as the anode.
The current is allowed to flow by switching on the current using a switch connected to the lead wires. The flow of current initiates a flow of electrons which starts up the electroplating process.
Observations are made in regard to the amount of copper deposited at the anode as well as the time taken.
Discussion
Copper is a metal, implying that it contains extra electrons in its energy levels. The copper sulfate solution used is also rich in Cu2 (aq).When the switch is closed, electrons flows from the DC source through the anode into the electrolyte. The ions are made to participate in the chemical process by establishing positive and negative potentials at either electrode which attracts them to the electrodes. The movement constitutes a flow which essentially facilitates electron flow which in turn induces a conventional current flow in the opposite direction. The flow of these electrons triggers a flow of the free electrons in the copper cathode which dissociates and goes into solution (Atkins, 1997). The chemical reaction that takes place at the cathode can be represented as
Cathode Cu2 (aq)  2e------- Cu(s)
This implies that the copper solid ionizes to its ions in the cathode resulting to its depreciation in mass. The padlock illustrated below is an example of an electroplated product.
Fig 2 the result of an electroplated padlock (the padlock was used as the anode)

Adapted from httpwww.made-in-china.comimage2f0j00TtEahVRMjQBCMElectroplating-Iron-Padlock-Chrome-Nickel-.jpg
The item to be electroplated obtains the color of the metal in the cathode whose electrons deposits and combines at the anode to form its solid form. The copper electrons that go into solution are negatively charged and they get attracted to the positively charged anode (containing the object to be electroplated).  The copper ions in the solutions plus the ions that dissociates from the copper electrode are attracted to the anode which is maintained at a positive potential from the DC power source. The chemical process that takes place at the anode can be represented as follows
Anode Cu(s) --------Cu2 (aq)  2 e-
The cupper solid formed at the anode is formed slowly at the surface of the object being electroplated and with time, a thin layer of copper layer is spread on the surface of the material being plated.  The amount of copper deposited is determined by Faradays laws of electrolysis. If the electrode being used was pure copper, then the electrolyte containing copper sulfate solution would consist of both water and the solution ions. (Water is used in making up the electrolyte). These ions are H, OH-, Cu2 and SO42-. The determination of the ion to be discharged at a particular electrode is determined by the chemical principle on preferential discharge that is determined by the element property especially its relative position in the reactivity series.

Cushings disease is a condition in which the body produces high amounts of the cortisol hormone (hypercortisolism) for long periods of time due to a rise in the levels of the pituitary ACTH hormone (Mayo, 2008).  The condition tends to occur more often in women compared to men, and in individuals between the ages of 20 to 60 years (Simard, 2004).  The ACTH Hormone controls the levels of cortisol and a rise in the ACTH by the pituitary would result in the adrenal glands secreting high levels of cortisol.  Cushings syndrome on the other hand can be due to consumption of oral cortisol medications or the hormone produced by several carcinomas or adenomas (Rakel, 2007).  There are certain peculiar characteristics of Cushing s disease including a moon-like face, a fatty hump behind the shoulders, pinkish stretch and obesity (Holt, 2009).    About 70  of all cases of Cushings syndrome are from Cushings diseases.  The condition usually develops over several months or years (Rakel, 2007).  In Cushings disease a range of clinical and biochemical features may be seen which arise mainly from the hypercortisolism (Simard, 2004). 
    There has been a lot of debate regarding the cause of Cushings disease.  There is intense debate whether the condition develops due to a pituitary abnormality or from a hypothalamic abnormality (Simard, 2004).  The hypothalamus may be involved in a way that chronic stimulation by the CRH hormone can result in high levels of the ACTH hormones by the pituitary resulting in a rise in the Cortisol levels (Katznelson, 1998).  There are several other studies which effectively demonstrate the problem lies in the pituitary gland and not the hypothalamus.  When the hypothalamus has been implicated, often ectopic CRH-secreting tumours have been suggested, but careful analysis through histopathology has demonstrated that the lesions are basically adenomas.  However, if careful analysis of the pituitary has been suggested, then it may be found that the CRH levels may in fact be normal when the cortisol levels are raised.  Other studies have demonstrated that the hypothalamus may have a role only during initiation of the condition.  However, further development and progression depends on the levels of secretion of the ACTH hormone.  In 85 to 90  of the time, Cushings disease is caused by a pituitary adenoma and in 9  of the cases by hyperplasia.  About 90  of all pituitary tumours from which Cushings disease is present are microadenoma (that is the tumour is less than 1 centimetre in size) and in 10  are macroadenoma (tumour over 1 centimetre in size).  When the tumour is larger in size, there are chances that it would be more aggressive in nature.  Tumours from other parts of the body including the adrenal gland or ectopic tissues can also result in the production of cortisol (Katznelson, 1998). 

Background Information
    The common symptoms of Cushings disease include obesity, skin infections, buffalo hump, hair growth, mental defects, purplish discoloration of the skin, weight gain, bone pain, tiredness, blood pressure rise, etc.   If the condition is not treated promptly, several complications may arise including diabetes, fractures, kidney stones, muscle dysfunctions and infectious (Holt, 2009).  Often the diagnosis of Cushings disease may be difficult for the clinician would rely on several laboratory tests.  The diagnosis of Cushings disease is made based on the history, symptoms, signs, physical examination, blood sugar levels (which may be high), white blood cell count (which may be increased), potassium levels (which may fall down), cortisol levels (which is increased), dexamethasone suppression test, ACTH test, pituitary MRI, abdominal CT scan, and urine tests (Mayo 2008).  When exogenous dexamethasone is given there is a diminished suppressibility of ACHTH and cortisol.  The symptoms of Cushings disease may fluctuate with the cortisol levels, and often it may be difficult to determine the hypercortisolism.  Early detection plays a vital role in treating Cushings disease.  When there is a pituitary adenoma of corticotroph the suppressibility of ACTH by corticosteroids is changed such that larger amounts of cortisol are required to lower the ACTH levels.  In most cases of pituitary adenomas, larger oral doses of dexamethasone in the range of 2mg every 6 hours for 2 days are required.  Smaller doses of dexamethasone will not suffice to lower the ACTH levels and bring the cortisol secretion by the adrenal glands within normal (Simard, 2004). 
Biochemistry
    As understood earlier, Cushings disease can be caused by a pituitary microadenoma and macroadenoma (these tumour release high amounts of ACTH stimulating the adrenal glands to produce and release cortisol hormone).  In macroadenoma, the tumour size is greater than 10 mm and in microadenoma less than 10 mm.  Both pituitary microadenomas and macroadenomas tend to occur at a similar age, but the urine free cortisol levels emitted in microadenoma was less than that emitted in pituitary macroadenoma.  In macroadenoma, the amount excreted was 1341 nmol per day whereas in microadenoma it was 877 nmol per day.  Higher amounts of 17-hydroxysteroid were emitted in macroadenoma compared to microadenoma.  Dexamethasone suppression tests were more effective for microadenoma compared to macroadenoma as the levels of 17-hydroxysteroid and urine free cortisol levels were brought down to a greater range in microadenoma compared to macroadenoma.  In 83  of the macroadenoma cases, the ACTH levels were above normal, compared to 45  in the macroadenoma cases.  Usually in case of Cushings disease, urine free cortisol levels should be measured two to three times to obtain precise results.  The body surface area should be corrected in children whilst performing the test, and in pregnant women the free cortisol levels emitted in urine would be higher.  The cortisol levels usually reach the highest level in the morning and the lowest levels before midnight.  In Cushings disease, the lowest levels may not be reached in the diurnal fashion (Katznelson, 1998).  This can be measured by doing a plasma test or a more sensitive way would be to do a salivary cortisol test.  A cortisol value of above 2 ng per ml of saliva helps to establish Cushings disease.  It is a very sensitive and specific test for Cushings syndrome.  Another test done for evaluation of Cushings syndrome is corticotrophin releasing factor test or CRF Test.  CRF is released by the hypothalamus and helps stimulate the secretion of ACTH.  An intravenous injection of 1 ml per kg body weight of CRF is given and the ACTH response of the patient is monitored.  Blood samples are collected every 15 minutes for about 2 hours.  Usually there is a normal response of 15 to 20  in the ACTH and the cortisol levels, but in Cushings disease, the ACTH levels rise to 50  and the cortisol levels to 20 .  In about 10  of the Cushings disease patient, no response to CRF may be obtained (Kronenberg, 2008).   Conclusion
    Cushings disease is treated based on the cause.  If the Disease is caused by a tumour of the pituitary glands, surgery to remove the pituitary, followed by radiation therapy and subsequent replacement of hormones for the entire patients life should be initiated.  If the condition is caused by an adrenal tumour, adrenal surgery and subsequent replacement of the adrenal hormones should be initiated.  However, relapses following the removal of the tumour should be anticipated and hence constant monitoring may be required (Holt, 2009).  Cushings syndrome if not treated can result in fatal outcomes.

 Radioactive material can be defined as any substance that consists of unstable radioactive particles that are able to emit radiation in the course of their decaying. Radioactive decay can be defined as the spontaneous loss of energy by a relatively unstable nucleus of an atom through the emission of ionizing atoms and radiation. In the process, an atom, usually referred to as the parent nuclide transforms to a different type of atom, commonly referred to as the daughter nuclide. Activity is measured in Becquerel (Bq). A single Bq. being equivalent to a single decay each second. Ionizing radiation is a type of radiation that has enough energy to dislodge electrons which are components of the atom. Some of the most common ionizing radiation includes x rays, gamma rays, beta rays and alpha rays.
    We are always exposed to radiation in our day to day lives. Each year, it is approximated that an individual citizen of the United States may be exposed to around 350 millirem of radiation. Millirem is a unit of measurement that is basically concerned with biological effects of the radiation we are exposed to. Such kinds of radiation are referred to as background radiation. Large quantities of ionizing radiation have been established to be very dangerous to living things and the environment, not excluding human.
    Skin cancer has been linked to radioactive materials right from the beginning since scientists working on them showed signs of skin cancer after sometime. Leukemia has also been established to be a consequence of the radiation. Indeed many other cancers can be as a result of radiation. Some of these include lung, liver, colon, prostate, pancreatic, laryngeal, nasal, breast, ovarian, bladder, stomach, esophagus, and multiple myeloma cancers. Ionizing radiations are able to alter the body cells since they can break electronic bonds that are responsible for holding molecules together. Radiation is able to damage our genetic materials (DNA). This is achieved by the displacement of electrons from the genetic material or from cells that interact with the DNA. This can lead to the destruction, growth or mutation of the cell. This can only occur on exposure to large radiation doses. Extremely large doses can even result to death. Large doses can also suppress the immune system or lead to cataracts.
    The radiation can be particularly harmful to the fetus. It can lead to lead to brain damage. The effects are able to affect generations of the affected individual. The radiations that are normally medically administered are always of low level and potentially less harmful. The body has mechanisms that can aid in adjusting from low level exposure. It is estimated that the optimum safe dosage of radiation is 10,000 millirem, beyond this value, there are bound to be harmful effects. Though, even lower dosage can be harmful depending on the body mechanism of the individual involved.
    The nuclear accident at the Three Mile Island took place on the 28th March 1979. This incident involved a partial meltdown of the reactor number two at the nuclear plant. It was alleged that a minor error led to the rise in main coolant temperature. The reactor automatically shut down. There was a relief valve which was meant to shut down after ten seconds but it did not. The main coolant of the reactor drained away, leading to damage on the reactor core. Fuel rods leaked radioactive material in the water that was meant for cooling. A reaction started that was aided by the high temperature that led to the evolution of hydrogen gas bubbles. There was fear of explosion so the gas was let into the atmosphere. It took about a whole month for the reactor to be brought to cold shut down. Vulnerable members of the society like children and pregnant women were evacuated. No major incidence arose as a result of the accident but it led to adjustments in the nuclear industry. The dosage was not so large.
    A disaster also took place in Chernobyl, which was part of the Soviet Union. It took place on 25th April 1986. It led to the death of an excess of thirty people. Workers were exposed to an excess of 80,000 millirem of radiation. Chernobyl had four types of reactors which were vulnerable to fast almost uncontrollable power increases. Tests were being carried out in reactor four. Only six rods were in place instead of the recommended thirty for the maintenance of control. Power dropped below the minimum required levels. This led to the rupturing of fuel rods. This led to explosions that damaged the reactor core. The health effects of the disaster cannot be quantified as it is thought that it will continue for some considerable duration of time. Several cases of thyroid cancer and leukemia have since been reported in the area.

 Radioactive material can be defined as any substance that consists of unstable radioactive particles that are able to emit radiation in the course of their decaying. Radioactive decay can be defined as the spontaneous loss of energy by a relatively unstable nucleus of an atom through the emission of ionizing atoms and radiation. In the process, an atom, usually referred to as the parent nuclide transforms to a different type of atom, commonly referred to as the daughter nuclide. Activity is measured in Becquerel (Bq). A single Bq. being equivalent to a single decay each second. Ionizing radiation is a type of radiation that has enough energy to dislodge electrons which are components of the atom. Some of the most common ionizing radiation includes x rays, gamma rays, beta rays and alpha rays (Johnson, 1999).
    We are always exposed to radiation in our day to day lives. Each year, it is approximated that an individual citizen of the United States may be exposed to around 350 millirem of radiation. Millirem is a unit of measurement that is basically concerned with biological effects of the radiation we are exposed to. Such kinds of radiation are referred to as background radiation. Large quantities of ionizing radiation have been established to be very dangerous to living things and the environment, not excluding human (Guttman, 2000).
    Skin cancer has been linked to radioactive materials right from the beginning since scientists working on them showed signs of skin cancer after sometime. Leukemia has also been established to be a consequence of the radiation. Indeed many other cancers can be as a result of radiation. Some of these include lung, liver, colon, prostate, pancreatic, laryngeal, nasal, breast, ovarian, bladder, stomach, esophagus, and multiple myeloma cancers. Ionizing radiations are able to alter the body cells since they can break electronic bonds that are responsible for holding molecules together. Radiation is able to damage our genetic materials (DNA). This is achieved by the displacement of electrons from the genetic material or from cells that interact with the DNA. This can lead to the destruction, growth or mutation of the cell. This can only occur on exposure to large radiation doses. Extremely large doses can even result to death. Large doses can also suppress the immune system or lead to cataracts (Johnson, 1999).
    The radiation can be particularly harmful to the fetus. It can lead to lead to brain damage. The effects are able to affect generations of the affected individual. The radiations that are normally medically administered are always of low level and potentially less harmful. The body has mechanisms that can aid in adjusting from low level exposure. It is estimated that the optimum safe dosage of radiation is 10,000 millirem, beyond this value, there are bound to be harmful effects. Though, even lower dosage can be harmful depending on the body mechanism of the individual involved (Guttman, 2000).
    The nuclear accident at the Three Mile Island took place on the 28th March 1979. This incident involved a partial meltdown of the reactor number two at the nuclear plant. It was alleged that a minor error led to the rise in main coolant temperature. The reactor automatically shut down. There was a relief valve which was meant to shut down after ten seconds but it did not. The main coolant of the reactor drained away, leading to damage on the reactor core. Fuel rods leaked radioactive material in the water that was meant for cooling. A reaction started that was aided by the high temperature that led to the evolution of hydrogen gas bubbles. There was fear of explosion so the gas was let into the atmosphere. It took about a whole month for the reactor to be brought to cold shut down. Vulnerable members of the society like children and pregnant women were evacuated. No major incidence arose as a result of the accident but it led to adjustments in the nuclear industry. The dosage was not so large (Guttman, 2000).
    A disaster also took place in Chernobyl, which was part of the Soviet Union. It took place on 25th April 1986. It led to the death of an excess of thirty people. Workers were exposed to an excess of 80,000 millirem of radiation. Chernobyl had four types of reactors which were vulnerable to fast almost uncontrollable power increases. Tests were being carried out in reactor four. Only six rods were in place instead of the recommended thirty for the maintenance of control. Power dropped below the minimum required levels. This led to the rupturing of fuel rods. This led to explosions that damaged the reactor core. The health effects of the disaster cannot be quantified as it is thought that it will continue for some considerable duration of time. Several cases of thyroid cancer and leukemia have since been reported in the area (Johnson, 1999).

Proteolysis of insulin in the endoplasmic reticulum followed by cleavage of the C chain of pro-insulin to form insulin is a good example of posttranslational modification. This paper looks at the insulin molecule, with a particular reference to its primary, secondary, tertiary and quaternary structures. Features of the protein which enable the molecule to perform its biochemical functions are also considered as are the posttranslational modifications and cellular activity. Structurally, insulin is organized at 4 levels the primary, secondary, tertiary and quaternary levels. It was found that insulin has 2 chains, the  and the  chains which are held together by disulfide bonds. The secondary structure is largely held together by van der waals forces and salt bridges. The quaternary structure of insulin consists of hexamers that arise from the association between hydrophobic surfaces. The molecule is first synthesised as preproinsulin and cleaved to form proinsilin and finally insulin. Insulin has tyrosine kinase activity and this enables the molecule to attach very tightly to its receptors and induce a series of phosphorylations which finally lead to the translocation of GLUT receptors and uptake of glucose by the target cells. It also leads to activation of the MAPK system.

Insulin is a protein hormone that is made up of 2 polypeptide chains and which has a molecular weight of 6kDa. Produced by the  cells of the islets of Langerhans in the pancreas, insulin is an active promoter of anabolic processes in the body. In this regard, insulin is associated with enhancement of the rate of glycogenesis, protein, and fatty acid synthesis. Insulin also enhances the uptake of glucose into muscle and adipose tissues and thus has a potent hypoglycaemic effect. Besides the anabolic effect, insulin also exerts a catabolic effect and it does this by reducing the level of enzymes that are necessary for such cellular processes as gluconeogenesis (Ganong, 1999)

. This paper discusses the chemistry and biochemistry of insulin with a particular emphasis on the synthesis methods, modifications (amino acid replacements, deletions, additions) and their effects. The role of metal ions in activation of insulin as well as the biochemical mechanisms underlying the function of this hormone is also discussed in an in-depth manner (Berg, Tymoczko,  Stryer, 2008)

The Primary Structure of Insulin
. The primary structure of insulin consists of 2 polypeptide chains called the A chain and the B chain. The A chain consists of 21 amino acid residues while the B chain consists of 30 amino acid residues (table 1 and 2). The 2 polypeptide chains are joined to each other via 2 disulfide bonds. These bonds are formed between the cysteine residues located on the 7th position of both chains and between the cysteine residue located on the 20th position of the A chain (Cys 20) and the cysteine residue on the 19th position of the B chain (Cys 19) (Berg, Tymoczko,  Stryer, 2008)

However, there is a variation of the composition of the chains depending on the species.

Secondary Structure of Insulin
The secondary structure of insulin is formed as a result of hydrogen bonds between the N-H and CO groups which jut out from the peptide bonds of amino acids situated 3 or 4 residues further along. The amino acid residue coil to create short sections of alpha helix and this helps to make the insulin molecule more stable.
The A chain has 2 turns of alpha helix between the isoleucine residue at position 2 and the threonine residue at position 8 (A2 Ile  A8 Thr) and between the leucine residue at position 13 and the tyrosine residue at position 19 (A13 leu-A19 Tyr). These 2 sections are separated by a flat ribbon that allows the 2 alpha helices to remain adjacent to each other and permits the creation of Van der Waals forces between the side chains of A2 Ile and A19 Tyr (Berg, Tymoczko,  Stryer, 2008). 

On the other hand, the B chain has a V shape arising from the alpha helix formed between the serine residue at position 9 and the Cysteine residue at position 19 (B9 Ser-B19 Cys) and between glycine residues at positions 20 and 23 (B20 Gly  B23 Gly). This causes the C terminal residues B24 Phe and B26 Tyr to associate with B15 Leu and B11 Leu via Van der Waals forces.

Tertiary structure of Insulin
    The tertiary structure of insulin consists of disulfide bridges which occur between the thiol groups (SH) of Cysteine. From the primary structure, it can be seen that there are a total of 6 cysteine residues at positions 6, 7, 11 and 20 on the A chain and at positions 7 and 19 on the B chain. From figure 1, it is evident that 3 disulfide bonds are formed and one of these occur in the A chain between A6 Cys and A11 Cys. The other 2 are created between the A and B chains between A7 Cys and B7 Cys and between A20 Cys and A19 Cys. Besides these disulfide bonds, the tertiary structure of insulin is also composed of numerous Van der Waals forces and salt bridges.

Quaternary structure of Insulin
The quaternary structure of insulin consists of hexamers that arise from the association between hydrophobic surfaces. Six insulin molecules band together around 2 zinc ions to create the hexamers. This structure has a toroidal shaped (i.e. it is shaped like a doughnut) and results in granules. It is in this form that insulin is stored in the pancreatic B cells and secreted into the circulation. Insulin can also exist in dimmers (2 units) or monomers (single units). Reportedly, insulin exists as a monomer in the active state.

Synthesis of Insulin
Human insulin is initially synthesised as a 110 amino acid single chain called the preproinsulin. This molecule is then converted to proinsulin by removal of the signal peptide.

Preproinsulin has 19 additional residues which are not present in the proinsulin molecule. These residues form a hydrophobic region which plays a vital role in the cleavage of the molecule into proinsulin. According to Berg, Tymoczko,  Stryer, (2008), this hydrophobic region acts as a signal sequence and causes the preproinsulin to move into the endoplasmic reticulum (ER). Once here, the hydrophobic region is cleaved off to form the proinsulin molecule.

The proinsulin molecule differs from the insulin molecule in that it has a third chain called the C-chain.  As can be seen in the sequence above, the C chain is composed of 30 additional residues which are absent in the insulin molecule. Figure 5 below illustrates the location of this C chain. It joins the amino end of the A chain and the carboxyl end of the B chain. There is a high degree of sequence homology between the C chains of proinsulins of different species. A common feature is that all the C chains have at their carboxyl ends arginine and lysine molecules at their amino ends 2 consecutive arginine molecules. Lysine and arginine are both basic amino acids with a net positive charge. It is these positively charged ends which form the cleavage sites for the proteolytic enzymes that cleave off the C chain. The lysine and arginine molecules occur at positions 62 and 63 respectively on the A chain of the proinsulin molecule in porcines while the 2 arginie residues are found at the 32 and 31 at the amino end of the A chain.
Conversion to insulin involves removal of this chain and the formation of disulfide linkages between the A and B chains.

Briefly, cleavage of the C chain involves transportation of the proinsulin molecule to the Golgi apparatus and to secretory granules where proteolytic enzymes cleave off the chain at the described positions.  Cleavage of the chain is mediated by the prohormone convertase 1 and 2 and results into an insulin molecule that has the 2 chains. Cleavage of the chain is followed by the removal of 2 amino acids are by the enzyme carboxypeptidase E.

Activity of Insulin
The tyrosine kinase activity of insulin has been well documented. To fulfil its functions in the body, insulin first of all binds to particular receptors which are localized on the plasma membranes of the target cells. The attachment of insulin to these receptors is very tight and this is central to the activity of the hormone. The receptor for insulin is made up of 2  and 2  chains. The  chains are 135 kd whereas the  chains measure 95 kd. These receptors are integral membrane glycoproteins and they innervate the plasma membrane, with obvious intracellular and extra cellular domains. In general,  chains occur principally on the extra cellular portion of the plasma membrane whilst the  chains are to be found inside the plasma membrane (Ottensmeyer FP et al, 2000).

Both chains originate from one main chain precursor which has a total of 1382 residues. The precursor molecule is made up of signal sequence, and the  and  chain sequences in that order. The  and  sequences are however separated by a tetra peptide which is composed of basic amino acids notably lysine and arginine. The common sequence of this tetra peptide is arginine-lysine-arginine and a final arginine molecule. This sequence plays an important role in the signal transduction pathway since it is recognized by the processing enzymes. The signal sequence is cleaved off and this activates the entire pathway. When activated, the insulin receptor acts as an enzyme and it phosphorylates tyrosine residues in the target proteins (Ottensmeyer FP et al, 2000).
On the cytoplasmic region of the receptor there are also tyrosine domains which occur largely in the B chains while the insulin biding sites are on the  chain on the portion of the membrane which is found on the outside of the cell. When insulin attaches to the receptor on the extra cellular the catalytic activity of the tyrosine kinase enzyme is turned on, leading to the phosphorylation of 2 tyrosine residues (Ottensmeyer FP et al, 2000).  
This is followed by the phosphorylation of the insulin receptor substrates (RS-IRS6). These are docking proteins and once they become phosphorylated, they attach to other kinases and activate them. Phosphatidyl inositol 3 kinase is the enzyme which is most often stimulated by the actions of the IRS proteins and these lead on to further phosphorylation which activate adaptor proteins. The most common adaptor protein which is turned on by the activity of the phosphatidyl inositol 3 kinase is the growth factor receptor binding protein 2 and this transduces this signal onto a guanine releasing factor. The latter molecule subsequently leads to the activation of the ras which is a GTP binding protein and mitogen-activated protein kinase (MAPK) system. These series of reactions constitute the second messenger system of insulin. The phosphorylation cause many effects, the most important of which is the movement of glucose transporters such as GLUT to the cell membrane and this causes the cells to increase their uptake of glucose (Nolte  Karam, 2007 Ottensmeyer FP et al, 2000).
Insulin is usually released from the B cells upon stimulation by glucose and mannose, amino acids such as arginine and leucine, and hormones such as the glucagons-like-polypeptide 1 (GLP-1). Release of insulin into the bloodstream can also be induced by certain drugs such as sulfonylurea (Dunning et al, 2005).

Figure  SEQ Figure  ARABIC 5 Control of insulin secretion
 Source Bertram (2008)

The transporters of Glucose


Source Katzung, (2007)
Insulin is processed in the endoplasmic reticulum where cleavage of the C chain from the proinsulin molecule occurs to form insulin. This is a prime example of posttranslational modification in eukaryotes. This paper looked at the insulin molecule, with a particular reference to its primary, secondary, tertiary and quaternary structures. Features of the protein which enable the molecule to perform its biochemical functions were also considered as were the posttranslational modifications and cellular activity. Structurally, insulin is organized at 4 levels the primary, secondary, tertiary and quaternary levels.