Biochemistry - How BSE Occurs at a Molecular Level - Coursework Example

Biochemistry - How BSE Occurs at a Molecular Level A.  The process of DNA replication at the biochemical level. B.  The role of the ligase enzyme in the replication of DNA. C.  The role of mRNA in transcription and translation. D.  The role of RNA polymerase inhibition in causing the poisonous effect of the death cap mushroom. Death cap mushrooms fall under a group of fungi known as Amanita phalloides, which are among the most poisonous fungi. Death cap mushroom poisoning occurs through RNA polymerase inhibition. When the activity of RNA polymerase is inhibited, the process of transcription fails to take place thereby leading to no production of mRNA. Subsequently, no translation takes place, and no protein is synthesised. As a result, vital biochemical reactions fail to take place since enzymes, which are biological catalysts, are made of proteins. In addition, cells die without being replaced by new ones, which eventually leads to death. 208.5.2-01, 02, 04-07 A.  Explain how BSE occurs at a molecular level. 1.  An original model of an essential amino acid with side chains. 2.  Two chemical characteristics (i.e., reactivity, toxicity, flammability, or hydrophobicity) of phenylalanine. Toxicity: Large amounts of phenylalanine taken in the form of nutritional supplements elevate blood pressure. Symptoms such as headaches, heartburn and nausea may be experienced. In addition, the nervous system is usually affected during toxicity of phenylalanine. Reactivity: Phenylalanine is a hydrophobic amino acid with an aromatic side chain. Therefore, it is fairly unreactive and mostly takes place in substitution reactions where it is interchanged with amino acids of a similar nature. Consequently, it plays a key role on substrate recognition rather than in protein function. 3.  An original diagram or series of diagrams of the different levels of protein structure and label the primary, secondary, tertiary, and quaternary structures. 4.  The formation of a peptide bond through dehydration. A peptide bond is made when the carboxyl end of an amino acid reacts with an amine end of a different amino acid. A water molecule is usually formed in the process. 5. How a peptide bond is broken through hydrolysis Adding a water molecule to a peptide bond breaks the bond leading to the formation of the two amino acids that initially formed the peptide bond. (Gozo, 2011) 6.  The four forces (bonds) that stabilize a protein’s three-dimensional structure at the tertiary level of protein structure. Hydrophobic forces: Non-polar amino acids aggregate in the interior regions of the protein due to hydrophobic effects. As a result, the interactions of non-polar residues with water are minimized. Electrostatic interactions: Oppositely charged amino acid residues interact to form salt bridges, which are mostly found on the surface of proteins. Hydrogen bonds: Hydrogen atoms from the amine groups are pulled towards the electronegative carboxyl groups leading to sharing of electrons. The repetitive nature of such attractions within the protein structure confers stability. Van der Waals forces: Interactions among induced dipoles that form from the changes in charge density that occur in adjacent atoms that do not necessarily form a bond constitute attractive van der Waals forces. Repulsive forces, on the other hand, entail interactions between atoms that come close to each other but do not form dipoles. The huge numbers of such forces within the structure of proteins affect the stability of proteins. 7.  The role of protein misfolding and aggregation in BSE. When certain proteins fail to fold in the required way, they begin to cluster and form aggregates. These aggregates contain certain polymeric structures such as beta sheets. In BSE, these aggregates are in the form of prions, which get into the brain and cause disease. 8.  The role of prions in BSE. Prions are proteinaceous infectious particles that comprise aggregates of misfolded proteins. Prions alter the structure of the brain by stimulating the formation of ‘holes’ in the brain, which ultimately give the brain a spongy architecture. Consequently, the nervous system is affected making the cow behave abnormally. Ingestion of prions present in contaminated food causes them to be taken up into the body. They then affect other normal proteins by influencing them to fold abnormally. 9.  The role of the chaperone protein in BSE. The chaperone proteins try to prevent the formation of aggregates or to reverse incorrect protein folding by directing the process of protein folding towards the native state (Horwich, 2002). B.  Recommendations for a country that does not have regulations in place can decrease the risk of BSE infecting the food source. Since BSE can be spread by eating contaminated food (food containing remains from an affected animal), I would recommend that this country puts measures in place to ensure that only healthy animals are slaughtered and made available to its population. I would also recommend that the government of such a country ensures that all food products do not contain brain or spinal cords from cattle. References Gozo, M. A. (2011). Orgo Lecture 4: Biochemistry & Lab Techniques. Retrieved from http://www.studyblue.com/notes/note/n/orgo-lecture-4-biochemistry--lab-techniques/deck/941910. Horwich, A. (2002). Protein aggregation in disease: a role for folding intermediates forming specific multimeric interactions. The Journal of Clinical Investigation, 110(9) 1221-1232. 208.5.3-01-05 A.  Hemoglobin 1.  An original model of hemoglobin that shows how oxygen is carried by the molecule. 2.  The major differences between the oxygenated and deoxygenated states of hemoglobin. In the oxygenated state, the proximal histidine residues as well as the helix carrying it change their positions because of the attachment of an oxygen molecule to heme. This leads to changes in the alpha-beta heterodimers to form the R (relaxed) state. In deoxygenated haemoglobin, the release of an oxygen atom causes a conformational change of the heterodimers to form the T (tense) state. Deoxygenated haemoglobin has stronger interactions within subunits, whereas oxygenated haemoglobin has weaker interactions between subunits. 3.  The Bohr effect for the association and disassociation of oxygen and hemoglobin. The Bohr effect is the reversible change in the affinity of haemoglobin for oxygen with variations in pH. a. An original diagram that demonstrates the relationship between oxygen affinity and pH. An increase in the amount of carbon dioxide decreases the pH of blood and causes hemoglobin to release oxygen. On the contrary, a reduction in the amount of carbon dioxide in the blood raises the pH of blood, which causes hemoglobin to take up more oxygen molecules. 4.  Original diagrams that compare the biochemical structure of hemoglobin to myoglobin. a. Clearly label diagrams to show the comparison.  B.  Sickle cell anemia 1.  A diagram that demonstrates the molecular (amino acid) difference between normal and sickle forms of hemoglobin. (Classical (Mendelian) genetics, n.d.). • A diagram that demonstrates the difference between normal and sickle red blood cells at the cellular level.  (Classical (Mendelian) genetics, n.d.). 2.  How the diseased cells are different from normal red blood cells in the context of their capacity to carry oxygen. Diseased red blood cells have a reduced capacity to carry oxygen compared to normal red blood cells due to their defective haemoglobin, which has a lower affinity for oxygen especially in low oxygen concentrations. Normal red blood cells have a lifespan of up to 120 days, whereas sickle cells have a life span of between 10 and 20 days. Normal haemoglobin possesses an oxygen-binding capacity of 1.34 mL O2. However, diseased red blood cells have only half of this capacity since the abnormality affects two subunits of the haemoglobin molecule thereby lowering its capacity to carry oxygen. 3. The molecular inheritance of sickle cell anemia. Sickle cell anaemia is caused by a change in the gene that is in charge of the formation of normal haemoglobin (HbA). This gene is found on the 11th pair of chromosomes. For an individual to have sickle cell anemia, he or she must possess both defective genes (HbS). However, an individual that has only one defective gene is a carrier. The inheritance of the disease occurs in an autosomal recessive manner. This means that the gene for the trait is found on chromosomes that play no role in determining the gender of the individual. As a result, males and females have an equal likelihood of inheriting the trait. (The Sickle Cell Association of Ontario, n.d.). References Classical (Mendelian) genetics. N.d. Retrieved from http://www.ptbeach.com/site/default.aspx?PageType=3&ModuleInstanceID=444&ViewID=7b97f7ed-8e5e-4120-848f-a8b4987d588f&RenderLoc=0&FlexDataID=348&PageID=907 The Sickle Cell Association of Ontario. (n.d.). About sickle cell. Retrieved from http://www.sicklecellontario.org/AboutSickleCell/AHistoryofSickleCellDisease.aspx 208.5.4-01, 03-05, etc A. To understand the issues behind hereditary fructose intolerance 1. How enzymes act as catalysts in biochemical processes (e.g., fructose metabolism, glycolysis). Enzymes change the rate of biochemical reactions by reducing the activation energy of reactions. A given enzyme must be specific to the substrate for the reaction to occur. Sometimes several enzymes may be necessary for a certain reaction to go to completion. In the metabolism of fructose, the enzyme fructokinase is required to convert fructose to fructose-1-phosphate, which is then converted to glyceraldehyde and dihydroxyacetone phosphate by the enzyme aldolase. The products of the reaction can then join the pathway of glucose metabolism (glycolysis). In hereditary fructose intolerance, absence of aldolase hinders the breakdown of fructose-1-phosphate causing it to accumulate. This accumulation hinders gluconeogenesis and production of ATP. This accumulation is what manifests as hypoglycemia, enlargement of the liver, jaundice and ultimate kidney failure. 2. How a deficiency in aldolase B can be responsible for hereditary fructose intolerance. Hereditary fructose intolerance is an inherited condition where one is unable to metabolize fructose due to the absence of aldolase. It is caused by an alteration in the gene that is in charge of the production of the enzyme aldolase B. Aldolase B catalyzes the conversion of fructose-1-phosphate into glyceraldehyde and dihydroxyacetone phosphate during fructose metabolism. Therefore, inheriting two copies of the defective gene causes the absence of this enzyme the development of hereditary fructose intolerance. 3. Clearly labeled diagrams that demonstrate the following: a. The lock and key model or induced fit model of enzymatic activity (Enzymes, n.d.). b. The effect of enzymes on activation energy (Enzymes (a), n.d.). 4. Discuss the specific substrate acted on by aldolase B during the breakdown of fructose. Aldolase B acts on fructose-1-phosphate during the breakdown of fructose. Fructose-1-phosphate comes from a phosphorylation reaction where fructose is phosphorylated in the presence of the enzyme fructokinase. The products formed from fructose1-phosphate by aldolase are dihyroxyacetone phosphate and glyceraldehydes. 5. The role of aldolase B in the breakdown of fructose by discussing the products of the reaction. The products of the breakdown of fructose-1-phosphate, which is generated from fructose, are glyceraldehyde and dihydroxyacetone phosphate. These products are then converted to energy or may be converted to glycogen for storage. For energy production, the products enter the glycolytic pathway. Therefore, aldolase B plays an important role in the utilization of fructose. B. How mitochondrial disease can occur at multiple levels in different mitochondrial processes by doing the following: 1. What would hypothetically happen to the amount of ATP available to a cell if the entire Cori cycle occurred and remained within that single cell (i.e., a muscle cell)? The Cori cycle involves lactic acid production by anaerobic respiration in the muscles, the movement of lactate to the liver. In the liver, it is changed back to glucose via gluconeogenesis. The glucose then finds its way to the muscles via the bloodstream where it is utilized anaerobically. The amount of ATP would be depleted ultimately if the cycle occurred in the same cell because some energy would still be needed during the conversion of lactate to glucose. Glycolysis expends 6 ATP molecules (from gluconeogenesis) and generates two ATPs. Therefore, each cycle uses up four ATP molecules. Therefore, if the cycle were to remain in one cell then it would be futile as it would still need 4 ATP molecules to sustain it. 2. An original dynamic diagram to show why the citric acid cycle is central to aerobic metabolism and how it leads to ATP production. The citric acid cycle is important in converting the acetyl-CoA from substrates such as glucose, proteins and fatty acids into NADH that can be used to generate energy in the electron transport chain. 3. Explain where in the citric acid cycle a hypothetical defect of an enzyme could occur that would decrease the overall ATP production, including the consequences of the defect. If a defect were to happen to the enzyme citrate synthase, the entire citric acid cycle would not proceed as all the reactions that depend on citrate would stop. The overall ATP production would reduce. In addition, the citrate machinery plays a role in the production of CoA, which is necessary in the formation of acetyl CoA to initiate the entire cycle. 4. The role of coenzyme Q10 in ATP synthesis as part of the electron transport chain. Coenzyme Q10 is needed in the synthesis of ATP in the electron transport chain. Electrons generated by NADH and succinate are passed to oxygen, which is consequently reduced to water. This process takes place in the interior membrane of the mitochondria. Hydrogen ions are propeled across the membrane by the transfer of electrons thereby generating a proton gradient. ATP synthase, which is situated in on the membrane, utilizes this gradient to generate ATP. Coenzyme Q10 works as an electron carrier by carrying “electrons from complex I (NADH coenzyme Q reductase) to complex III (cytochrome bc1 complex) or from complex II (succinate dehydrogenase) to complex III” (Molyneux et al., 2008, p. 71). References Enzymes. (n.d.). Retrieved from http://www.vce.bioninja.com.au/aos-1-molecules-of-life/biochemical-processes/enzymes.html Enzymes (a). (n.d.). Retrieved from http://www.4college.co.uk/a/ep/enzyme.php Molyneux, S. L., Young, J. M., & George, P. M. Coenzyme Q10: Is there a clinical role and a case for measurement? The Clinical Biochemist Reviews, 29(2), 71-82. 208.5.6-01-05 A.  Part 1: 1.  How lipids can lead to ATP production. Lipids can lead to ATP production by first going through hydrolysis to yield fatty acids and glycerol molecules. The fatty acids then undergo beta oxidation to produce Acetyl-CoA. Acetyl-CoA then enters the citric acid cycle where it is converted to NADH and FADH2. NADH and FADH2 then get into the electron transport chain where ATP is produced. 2.  Comparing saturated and unsaturated fatty acids. Unsaturated fatty acids have a double or bond between adjacent carbon atoms, whereas unsaturated fatty acids have no double bond between adjacent carbon atoms bonds Some fatty acids have more than one double bond and are called polyunsaturated fatty acids Unsaturated fatty acids are liquid at room temperature, whereas saturated fatty acids are solid at room temperature Saturated fatty acids are mainly found in animal products while unsaturated fatty acids are mostly obtained from plant products Unsaturated fatty acids have double or triple bonds, whereas unsaturated fatty acids have no multiple bonds. a. Original 3-D models to demonstrate the chemical structure of a saturated and an unsaturated fatty acid. B.  Part 2: 1.  The role of fatty acids in the body. Fatty acids provide energy to the brain in addition to glucose and ketone bodies. Fatty acids are also important in the formation and maintenance of cells and cell membranes as well as nerves (Neitzel, 2010). Fatty acids constitute the building blocks of other essential components such as glycolipids and phospholipids. Some hormones, which are chemical messengers, are made up of products of fatty acids. Fatty acids serve the role of targeting molecules by being attached to proteins thereby enabling certain proteins to reach specific parts of the cell through the cell membrane. Fats enable the body to utilize certain nutrients. Fat-soluble vitamins, for example, are properly utilized in the body in the presence of fats. Fatty acids form fats which often cushion delicate organs inside the body, for example, the heart and kidneys. 2.  A diagram that demonstrates the fluid mosaic structure of cell membranes. (Fluid Mosaic Model of Cell Membranes, 2004).  C.  Part 3: 1.  How no-fat diets can affect the biochemical functions of the body. No-fat diets can affect the biochemical functions of the body in different ways. Cell membranes can lose their integrity due to lack of fats. The transmission of chemical signals can also be affected by lack of fats since fatty acids make up hormones. As a result, numerous other biochemical functions may come tom a standstill. Transmission of nervous impulses can also be affected when an individual consumes a fat-free diet for a prolonged period since nerve cells will be affected. References Neitzel, J. J. (2010). Fatty Acid Molecules: Fundamentals and role in signaling. Nature Education 3(9), 57-65. Fluid Mosaic Model of Cell Membranes. (2004). Retrieved from http://www.biology.arizona.edu/cell_bio/problem_sets/membranes/fluid_mosaic_model.html Read More