The Biochemical Overview of Sickle Cell

Running Head: The Biochemical Overview of Sickle Cell

The Biochemical Overview of Sickle Cell: The Analysis of the Inheritance and Treatment of the Sickle cell disease Chemically and Biologically Keshia Rayford IDS 401 Dr. Allan Eickelmann University of Southern Mississippi September 25, 2013

The Biochemical Overview of Sickle Cell

Abstract This paper is to discuss the inheritance and treatment of the human disease Sickle cell biochemically. The aim of this research is to analyze the aspects of Biochemistry when inheriting and treating the human disease sickle cell. This paper will further examine how biochemistry aid in maintaining the health of a patient with sickle cell. The methodology approach that used is qualitative, focusing on questionnaires from students who is either currently studying or has studied biochemistry, chemistry, and/or biology. I also intend on sending questionnaires to teachers that are either teaching or has taught biochemistry, chemistry, and/or biology. All the answers will be reviewed in effort of understanding how biochemistry analyzes the inheritance and treatment of sickle cell. The disciplines Chemistry and biology are combined in effort to support the biochemical overview of sickle cell.

The Biochemical Overview of Sickle Cell

Introduction The basis of science and all the different levels of science have a big role in the medical field. In the medical field the main three branches of science are anatomy, biochemistry and physiology. Biochemistry, commonly referred to as chemical biology, is the study of chemical process within living organisms. Biochemistry has become the one of the focal points of explaining the processes that occurs within living organisms. Medically, biochemistry plays a huge part in exploring the causes and cure of diseases. It is associated with the structures, functions and interactions of proteins, nucleic acids, and carbohydrates. When discussing the human disease sickle cell anemia, which is a genetically inherited disease, it is not a surprise that biochemistry has a huge integral part in discovering and treating the disease sickle cell. What does biochemistry have to do with sickle cell? Well, simply put biochemistry is closely related to molecular biology, which involves encoding genetic information to DNA.

The Biochemical Overview of Sickle Cell

Literature Review When discussing the relation between science and medical related issues, such as diseases, it is obvious as to how the medical field benefits from the world of science. The human body is undergoing changes and reactions all through the day. There is never a moment when our body is not reacting with some sort of outside mechanisms. Generally, the human body is organized into six levels that collectively maintain the health of the body. The body functions at a chemical, cellular, tissue, organ, system and organism level. At a chemical level, the body is normally made up of 26 different chemical elements and 96% of the bodys mass is made up of oxygen, carbon, hydrogen, and nitrogen. The remaining percentage 4% consists of trace elements (0.2%) and calcium, phosphorus, potassium, sulfur, sodium, chlorine, and magnesium, and iron (Hendry, Fairley, & McLafferty, 2012). Sickle cell disease as stated before is an inherited disease, plainly stated it is caused by a mistake in the chemistry of the body. It is the result of abnormal hemoglobin, which is the oxygen-carrying molecule of the red blood cell (Bloom, 1995). Biochemistry deals with biological macromolecules such as proteins, nucleic acids, carbohydrates, and lipids which all help with the structure of the cells in the body as well as all the functions associated with the human body. Why is this relevant to sickle cell? Simple, the gene for hemoglobin produces a protein that is different by one amino acid (Biggs, Gregg, Hagins, Kapicka, Lundgren, & Rillero, 2002). Biochemically, the hemoglobin (Hbs) molecule loses oxygen and becomes deoxygenated which causes it to undergo polymerization and this is what causes the sickling of the red blood cell (Alayash & Bonaventura, 2010). The sickle hemoglobin is a result of the single point mutation of the glutamic acid (Glu) to valine (Val) on the sixth codon of the beta chain. Figure 1 shows the diagram of the Hb A gene (normal) and the Hb S gene (mutated).

The Biochemical Overview of Sickle Cell

Figure 1 Figure 1 shows how the normal red blood cells look and the picture to the right shows how the red blood cell looks after it becomes deoxygenated. The second picture shows the point mutation of Glutamate to Valine and it also shows the individual characteristic of each amino acid.

Individuals that contain two of the affected beta chain will develop sickle cell disease. Individuals that are heterozygous for sickle cell will carry the trait and remain without symptoms of the disease. Biochemistry does study the molecular mechanisms by which genetic information encoded in DNA is able present life. Therefore, biochemistry helps with detailing the process and how sickle cell is inherited (Gong, Paikh, Rosenthal, & Greenhouse, 2013). The sickle cell trait runs in the same family as the sickle cell disease. The infected gene will be passed on by either one of the parents or both. It was also questioned and tested in research that the mothers were quite frequent to pass the trait to the child but it was later rejected because there isnt anything that supports the findings (Ingram, 2004). When discussing biochemistry and all the things that contribute to the overview of sickle cell genes (genetic

The Biochemical Overview of Sickle Cell

information) is a vital part to discuss. Genes are considered to be the blueprint of the body because they carry information by the use of DNA, which forms a double helix. As stated previously the genes for hemoglobin damaged which makes them abnormal. The inheritance of the disease sickle cell disease is about chance. It is never certain what genes from the parents are transmitted to the child. Half of each of the parents genes makes up the genetic makeup of the child. Genes play a big part in the inheriting of sickle cell because genes include all the information and instructions for making all the body proteins. Some of the major proteins in the human body serve as the building materials of the body and others may serve as enzymes. When the disease is inherited it is passed on to the child as a pair and biochemically genes come in pairs, known as alleles, that are attached to paired chromosomes. There is more than one allele on one chromosome which is why it is so high for a child to inherit the trait from the parents. All the alleles in the human body determine the genetic makeup of an individual. When discussing the biochemistry of genes its difficult to understand without understanding the knowledge of recessive and dominant. Some genes are codominant (having sickle cell) and recessive (having the sickle cell trait). Genetically, genes have two roles: they have the ability to duplicate so that they can be passed from generation to generation and by directing the production of proteins (Bloom, 1995). Patients that were homozygotes for the mutated gene suffered from the disease and experienced severe pain. This pain was because of the shape of the sickled-shaped cell it was unable to flow through the capillaries without becoming trapped (Alayash & Bonaventura, 2010). In sickle cell the hemoglobin, which is enclosed in the red blood cell, becomes deoxygenated and transporting oxygen to the other organs in the body becomes hard. A look inside in the red blood cell will also show the connection that biochemistry has with the sickle cell disease. Typically the red cell is an oval shape molecule that contains hemoglobin. The red blood cell transports the hemoglobin to its designated area. Compared to the other cells in the human body, the red blood cell is different. It is incapable of reproduction and does not contain a nucleus. The red blood cell is made by stem cells in the bone marrow. This is important biochemically because this helps with the treatment of sickle cell (Bloom, 1995).

The Biochemical Overview of Sickle Cell

As mentioned earlier, biochemistry is used in medicine to explore the causes and cures to diseases in the body. As of now, there is not a cure for the disease sickle cell but the symptoms can be treated. There are many researches being done in effort to come up with a cure. The current research involves the following: (1) the development of anti-sickling agents, (2) turning on the genes that increase the production of HB F, (3) bone marrow transplantation, and (4) gene therapy. All of the previous stated possible cures create a direct connection between biochemistry and the disease sickle cell (Bloom, 1995). Stem cell transplantation was for patients with a severe case of the sickle cell disease because this was a very dangerous procedure and it did not always work (Thompson, Ceja, & Young, 2012). When a women becomes pregnant there are more measures that need to be taken to ensure the safety of both the mother and child. If a mother to be already has the disease then they are likely to suffer more pain and is at risk of multi-organ complications ( (Esegbona-Adeigbe, 2013). When it comes to biology and chemistry supporting each other in the inheritance and treatment of the disease sickle cell, it is true. Both subjects are connected together to use biochemistry to analyze the relation between them all. Sickle cell is caused by a error with the body genetic makeup which is all a part of the chemistry of the human body. The management and caring for someone with the human disease sickle cell has improved a great deal in the past couple of decades. The modernization of medical care is allowing the people with the disease to live longer, more comfortable, and they are also able to live a more productive life. The modernization is not the only reason for the improvements in management and care, because the people has been educated more on the disease and made aware of a lot of things it has decreased the dangers and eased the pain. Patients as well as family members are aware of how to handle and treat the person affected with the disease. There are

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many options that are offered to the people with the sickle disease as well as their family. Genetic counseling and advanced family planning is offered to those families that hoping to have children but are afraid of the possibility of passing the trait to their child. After a child is diagnosed with sickle cell, medical care is made immediately with the doctor. It is extremely important that the sick patient is cared for by medically and it also important to understand how to care for those in the privacy of their or your home. It is very important that the instructions that were given by the doctor be followed at all times. Care-givers should be fully aware of the dos and donts such as the proper diet, adequate fluids, prescribed medications, appropriate dayday-to-care, and keep a watchful eye. It is very likely that patients with sickle cell disease experience painful episodes and sometimes these episodes can be handled with medication from home or the patient may have to be hospitalized. That is why it is vital for whom ever is acting as care giver be fully aware of all the possibilities and responsibilities comes with caring for a patient with sickle cell. As previously mentioned, it is critical that the patient maintain a proper diet. It is best that the patient eat a high calorie diet because sickle cell patients tend to have a high metabolic rate. When we eat our body uses nutrients to help with maintaining a healthy body and it also help with growth. However, the nutrients that are consumed in a sickle cell patient are used first to make new red blood cells to replace the damaged cells that are being destroyed constantly. That is why it is important to make sure that all nutrients are being consumed because the body has to work extra hard to replace destroyed red blood cells. Doctors or physicians may even recommend that vitamins be taken to ensure that the patient is consuming the amount of nutrients needed daily. The amount of fluid is also important but it is most important when the individual is experiencing pain. It is encouraged to consume more fluids than normal when they are experiencing pain because this indicates that the blood vessels

The Biochemical Overview of Sickle Cell

are clogging somewhere, the additional fluid might assist with the getting the blood to flow again. The amount of fluid intake is also important when the individual has a fever because it could indicate an infection of blood vessel blockage as well. Having a fever causes the body to lose water and the increase of fluids would decrease the possibility of Hb S polymerization. For a patient with sickle cell, it is extremely important to consume more than normal. Caring for a person with sickle cell is a full time job itself. It requires a lot of attention, understanding, patience, and calmness. There is no cure for the human disease sickle cell at the moment but it does recommend that a healthy individual keep the stress level down, eat a high metabolism diet that is high in protein, and most importantly consuming an adequate amount of fluids daily (Bloom, 1995).

The Biochemical Overview of Sickle Cell

Statement of Methodology The methodology that is used for this research is a qualitative research, including questionnaires. As my research prevailed, it was clear that the only people that were able to answer the questions were the one that were familiar with biochemistry and/or sickle cell. There were a total of ten questions that were sent to the participants and their answers would be compared and used to see the connection with biochemistry and the human disease sickle cell. The questions collectively will be able to give insight and only strengthen the research for this paper as well as detail the relationship between chemistry and biology when discussing the discovery and treatment of sickle cell. All participants were informed orally and written of their rights while participating in this experiment. All the participants were emailed the following: You are receiving this email because you have electronically agreed to participate in a research conducted by me, Keshia Rayford. The answers to the following questions will remain anonymous and will only be referred to by your title such as, Doctor, professor, or student. The following questions will be used in a research project to help Keshia Rayford obtain a degree from the University of Southern MS. The questions are general questions about the topic of this research which is, A Biochemical Overview of Sickle Cell: The Analysis of the Diagnosis and Inheritance of the Sickle cell disease. Your responses will be used to strengthen my research project and your responses may generate new questions. I will email you any questions that may arise from your responses. If at any point you have any questions concerning the research project please feel free to email me at keshia.rayford@eagles.usm.edu. Thanks for your participation.

The Biochemical Overview of Sickle Cell

1. Based off your knowledge can you provide a brief summary of the study of biochemistry, biology, and chemistry? 2. When discussing biology and chemistry, would you say that biochemistry is a good way to show the relevance between the two and if yes explain? 3. Science is a big part of the medical field. Can you provide how biochemistry supports the medical field when it comes to the human body? 4. Do you feel that biochemistry and genetics have a connection with discussing inherited diseases? 5. Being more specific can you explain how biochemistry explains the inheritance of sickle cell? 6. Biochemistry is used in medicine to explore the causes and cures to diseases in the body. Do you feel that the previous statement is true and why? 7. Based off your knowledge, briefly explain red blood cells and function in the human body? 8. Can you take me inside of a red blood cell? What is going on once it becomes deoxygenated and how it affects the patient body? 9. There are several researches being done in effort to find a cure. Can you briefly discuss the relation between biochemistry and one of the following possible cures? a. The development of anti-sickling agents b. Turning on the genes that increase the production of HB F c. Stem cell transplant d. Gene therapy

The Biochemical Overview of Sickle Cell

10. Do you feel that biology and chemistry support each other when discussing the inheritance and treatment of sickle cell? Explain.

The Biochemical Overview of Sickle Cell

The Execution In executing this research design, I began my research on gathering and studying the human disease sickle cell. Considering that my disciplines were chemistry and biology, I needed to have a more in depth understanding of both topics separately. I am fully aware of the knowledge of both but I wanted a more detailed understanding and by looking it at a medical stand point. After I completed a more in depth research on both biology and chemistry, I wanted to find common ground between the two when discussing human diseases such as sickle cell. I wanted to find a way to discuss the biological overview of sickle without having to talk about each subject individually. I eventually decided that the best way would be to discuss the biochemistry of sickle cell. By studying the biochemistry of sickle cell, I thought it would allow me to look at both concentrations and open the door for more insights on sickle cell. Once all my research was gathered, it was time to put it all into perspective. This was the hardest part of executing my research, mainly because it was a lot of information that needed to be grouped by topic and content. Once all the information was correctly grouped and outlined so that the paper would be easier to write, I had to refer to the information researched to decide on how I would use the information to help with the creation of questions to be given to the participants. All participants were emailed and/or mailed a letter that informed them of the research that was being conducted and asked for their permission to release any information obtained for the purpose of this research. It was rather difficult trying to organize all the information but it was done successfully. After all the questionnaires were returned, it was time to create a common ground amongst the participants. All the participants answers were revealed and researched even further to strengthen the background information already gathered. Once common ground was established the rest of the research was a matter of putting it all together.

The Biochemical Overview of Sickle Cell

The Conclusion After completing my research and reviewing all the answers to the research questions from the participants. Biochemistry can be used to discuss the biological and chemical aspects of the human disease sickle cell. A professor from The University of Southern MS stated that the big improvement in understanding the physiology of the human body has provided a clearer picture of the activity within the body at a chemical level. A lot of the available treatments today are occurring at a chemical level. As of today there is no cure for the human disease sickle cell but there are many researches being completed in effort to find a cure. A pre-med major student from The University of Mississippi discussed how biochemistry could be used to explore a possible treatment. The possible treatment that was discussed was the stem transplant, which is simply replacing the stems cells that was responsible for red blood cell production. Biochemically, it is the removal of the source of mutation that alters the hemoglobin causing the cell to sickle and replacing it with a correct gene copy. The professor (USM) discussed the treatment that allowed the fetal hemoglobin genes (Hb F) to be turned on or activated. This treatment is the most promising for those that suffers from the sickle cell disease. Increasing the Hb F gene does not exactly provide a cure but it can inhibit the chance of sickling which would decrease the pain episodes someone may experience. According to the professor, the fetal hemoglobin gene are to replace or supplement as many of the mutated hemoglobin genes. This particular treatment may be the most promising but it does has a downfall. While turning on the Hb F genes, other genes might also be turned on, including genes that cause cancer. I feel that collectively the results from my research have allowed me to understand sickle cell in depth. I have gained a better range of how the hemoglobin inside the red blood cell functions and how biochemically this supports the overview of sickle cell

The Biochemical Overview of Sickle Cell

Future Implications I feel that that there are few models that I can discuss to depict my understanding of my research visually. To help me explain the inheritance of the sickle cell disease, I would refer to Professor Reginald Crundall Punnett diagram of the punnett square in attempt to see the possible offspring outcome when both parents alleles are crossed or breed together. By using a punnett square to discuss the inheritance is reliable because it is allowing me to see all the possible outcomes of the parents children and the children offspring as well. The following diagram is an example of punnett square:

Figure 2 The above illustration (Figure 1) shows how the alleles of the offspring can be determined. Across the very top of the diagram is the mother and her dominant and recessive alleles listed and along the left side of the diagram is the father and his dominant and recessive alleles. In order to get the offspring genes a gene is taken from both parents to determine the alleles of the offspring.

The Biochemical Overview of Sickle Cell

I would be able to see who would likely carry the trait and who would likely have the disease. Another familiar model to help me visually see what I have learned to understand would be the DNA molecule. In discussing the inheritance, genes that are close together on the same chromosome are usually inherited together. Therefore, anyone that is related will not only share the same Hb S gene but the neighboring genes as well. The following diagram is how a DNA molecule looks:

Figure 3 Figure 2 is a diagram of the double stranded DNA molecule. This molecule will produce RNA, who then produces the proteins that are associated with the human disease sickle cell. The biochemical difference in the protein chain in the hemoglobin of the disease sickle cell is what displayed the change of the amino acids. Taking a look at the polypeptide of someone with the sickle cell disease, without it, and someone that just has the trait will discover the chemical

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properties of the protein chain in the hemoglobin of the disease sickle cell. The following illustration shows the difference of the three:

Figure 4 I feel that all the above illustrations help me to understand my research visually. I can see how a normal red blood cell looks versus one that is sickle cell. It helps me to understand what it means when it says it becomes deoxygenated; I can physically see the inflation of the red blood cell. I am able to understand how the hemoglobin is related to biochemistry by looking at the chemical characteristics of it (figure 4). The models helped me to see what I learned visually, it allowed me to comprehend, capture the unity and coherence. (Lewis)

The Biochemical Overview of Sickle Cell

Annotated Bibliography

Alayash, A. I., & Bonaventura, J. (2010). The Biochemical basis of Sickle Cell Anemia in Saudi Arabia: A Model Case of Genetic and Molecular Disorders. Biochemical Education , 2-5. This article detailed the biochemical aspect of the disease sickle cell. It emphasized on all the biomolecules that are associated with the sickle cell disease. Biggs, A., Gregg, K., Hagins, W. C., Kapicka, C., Lundgren, L., & Rillero, P. (2002). Complex Inheritance of Human Traits. In Biology: The Dynamics of Life (pp. 329-330). Columbus: Glencoe McGraw-Hill. This article talked about how the sickle cell disease was inherited. It also briefly discussed how the disease is treated in people with sickle cell disease. Bloom, M. (1995). Sickle Cell Disease. Jackson: Unviersity of Press of Mississippi. This book focused on every aspect of the disease sickle cell. It detailed the inheritance, cure, treatment, and how to maintain life with the disease. The book provided a detailed description of the red blood cell and how the hemeglobin becomes deoxgenated. Esegbona-Adeigbe, S. (2013). Care of the Woman with Sickle cell disease in pregnancy. British Journal of Midwifery , 464-471. This article detailed how preganant women can get a test performed during pregnancy that will reveal if the fetus will be a carrier of the disease or if they will inherit the disease. It also discusses the care that pregnant woment should receive while carrying a child and they have the sickle cell disease.

Gong, L., Paikh, S., Rosenthal, P. J., & Greenhouse, B. (2013). Biochemical and Immunological mechanisms by which sickle cell trait protects against malaria. Malaria Journal . This article briefly discuss the overview of sickle cell and how it can be used to prevent other diseases in the body.

Hendry, C., Fairley, A., & McLafferty, E. (2012). Introduction to the life Sciences setious and honeostatasis. Nursing Standard , 46-50. This article talks about how the body maintain homeostatsis when the body is compromised with a disease. It also discusses the different

The Biochemical Overview of Sickle Cell Ingram, V. M. (2004). Sickle-Cell Anemia Hemoglobin: The Molecular Biolog of the First "Molecular Disease"-The Crucial Importance of Serendipity. Genetics , 1-7. This article discusses how the disease is first discovered and how it was used in the laboratroy for testing. It also talks about the possible treatments for the pain that a sickle cell patient may have. Thompson, L. M., Ceja, M. E., & Young, S. P. (2012). Stem cell transplantation for treatment of sickle cell disease: Bone marrow versus cord blood transplants. American Society of Health-System Pharmacists , 1295-1301. This article discusses the treatment of sickle cell. It mainly discuss the treatment using stem cell transplatation. It talks about all the pro and cons of performing stem cell transplantation.