Who mutations create sponge like holes that destroy
Who would of thought that eating hamburgers, steaks and drinking milk could produce an epidemic disease?These types of food are frequently eaten for their appealing tastes and nutritional values.The discovery of Creutzfeld Jakob Disease (CJD) has been a long and remarkable one.The cause of this disease is a mutated prion protein within the brain that can be either inherited or acquired.
These mutations create sponge like holes that destroy the brain.As a result, the disorder gives both behavioural and muscular problems to infected individualsExperiments and discoveries to this disease have led to a further understanding of the diversity of proteins. In the 1960s, D. Carleton Gadjusek studied the behaviour of a native population in Papua, New Guinea. This population had been eating the brains of dead relatives and as a result, contracted a fatal neurodegenerative disease. When autopsies were taken from the population who died, they appeared to have a distinct pathology.
The central brain tissue resembled a sponge with a lot of regions containing microscopic holes. The results of this disease appeared similar to persons affected with CJD. In 1968, D. Carleton Gadjusek injected an infected biopsy of brain with this disorder into a laboratory animal. As a result, the animal developed this disease. At this time, the biopsy was thought to contain a virus.
At the University of California, Stanley Pruisner and colleagues proposed that agent for this disease was a prion. A prion is a protein version of viruses without the genetic information.Once the prion has entered the body, the normal proteins are mutated. The gene for the normal protein is expressed within normal brain tissue and encodes a protein that resides at the surface of nerve cells. The function is unknown.
The mutated prion version of the protein accumulates within nerve cells, forming aggregates that kill cells.The normal protein is soluble in salt solution and is destroyed by protein-eating molecules, known as enzymes. However, the mutated prion protein is insoluble and the protein digestion. Based on these differences, one might expect these two forms of the prion protein to be composed distinctly different sequences of amino acids, but this is not the case. Prions are proteins, a diverse group of macromolecules. Proteins are capable of a wide variety of functions and activities. This is due to the great variety of structures.
Proteins are polymers of amino acids known as polypeptides.These amino acids are the structural building blocks of proteins.Amino acids have a single carbon linked to: an amino group, a carboxylic acid group and a side chain.These side chains vary in structure and determine the chemical properties of the amino acids.
Each protein has a unique and highly ordered structure that is highly specific with the molecules it interacts with.The assortment of the twenty amino acids are important because of the activities the protein can perform in terms of both the intramolecular interactions and intermolecular interactions. Intramolecular interactions are the forces within a molecule.It could be thought of as intramural collegiate activities, interactions within a molecule. Intermolecular interactions could be thought of as intermediate collegiate activities, interactions outside the molecule and this.
During the process of protein synthesis for the normal and mutated prion, special bonds known as peptide bonds form a polypeptide chain.There are several levels of organization that can describe the structure and reactivity of this prion protein.The primary structure is the specific linear sequence of amino acids that constitute the chain.For both the normal and mutated proteins, the primary structure is the same.This sequence of amino acids is very important in both the structure and function of the proteins.Even though the primary structure of any protein is unique, the secondary structure of many different proteins can be the same.These are selected regions that have protein structures that are repeated throughout the polypeptide chain.
In terms of the secondary structure, both the normal and mutated proteins are still the same.With respect to the secondary structure, hydrogen bonding is a very important type of intermolecular force that determines the structure. One type is the alpha helix that is a right-handed coil that is threaded in the same direction as a standard wood screw.
The helical structure of a polypeptide results from hydrogen bonds between elements of peptide bonds that are distributed along the backbone of the chain.Another type of is beta-pleated sheet that are completely extended and lie next to one another.They are stabilized by hydrogen bonds between the elements of the peptide linkage.
Tertiary structure of proteins is a result of the folding and twisting of polypeptides through intermolecular interactions. This results in the creation of specific shapes of polypeptide molecules. The intermolecular interactions are a result of hydrogen, ionic and covalent interactions.The chemical nature of side chains on individual amino acid determines how the molecule folds and packs in three dimensions.At this point, this is where the normal and mutated proteins differ in their structure.
Moreover, both proteins have the same primary and secondary structure, however, it is the tertiary structure that is different. This level of organization changes the role that the protein plays in an organism; from normal protein to a life-threatening mutated protein. The mutated prion protein can be both inherited and acquired.
When the mutated prion is an organism, the normal prions are mutated. Stanley Pruisner proposed a mechanism where mutated prion protein acts as a template for the normal protein to mutate. The mutated prion protein happens to be susceptible to folding incorrectly normal proteins and this accumulation happens to cause the death of cells in which it occurs. In an experiment to test this mechanism, the addition of a small amount of normal prions with small amount mutated prions form, showed that all of the components were expressed as the mutated form.Thus, the mutated prion protein initiates a chain reaction that mutates the normal prion.In the late 1980s and early 1990s, scientists believed that mad cow disease (scientific name Bovine Spongiform Encephalopathy, BSE) only affected cattle.
At this point, the mad cow disease was believed to be an inherited disorder.However, during the mid-1990s, a deadly version of mad cow disease known as Creutzfeldt-Jakob disease (vCJD) infected the people of UK.After this incident, experts believed the disease was also transmitted through the food chain.
To date, fifty-six people in the U.K. died by vCJD.Several scientists in England and Switzerland have been studying the scrapie disease, a disease similar to vCJD and BSE, in mice.In the experiment, mutated prions were injected into the bellies of mice. The prions initially infected the spleen and lymph.
Signals were initiated from a molecule called Lymphotoxin (LT) alpha/beta on the surface of immune cells to the spleen and lymphs immune cells.These signals mutated the normal prions to the disease-causing ones.If these signals were somehow blocked, then the normal prions will not be mutated.Scientists tested this hypothesis by injecting a molecule that forms a bond to lymphotoxin-alpha/beta into the injected mice.The molecule blocked any signals from immune cells to the spleen and lymphs immune cells.
By preventing the prion from mutation, the disease did not spread as fast.In addition, when the mutated prion was blocked from the central nervous system, there will be no sign of the disease.As a result, the mice who were treated with this molecule seem to develop the scrapie disease much later than the untreated mice.Even though scientists have not developed a cure for the disease, these findings show a lot of promise to the medical community.If the disease is treated at its initial stages, the disease could be suppressed and eventually it could be cured.
Ultimately, each new discovery about a disease is a step closer to the ultimate goal, a cure for a disease. Bibliography:BibliographyAlberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD. Molecular Biology of the Cell, 3rd Edition. New York: Garland Publishing, Inc., 1994.Chesebro, B. 1998.
BSE and prions: Uncertainty about the agent. Science 279: 42-43.Cousens, S. N., et al. 1998.
Predicting the CJD epidemic in humans. Nature 385: 197-198.Harris DC.
Quantitative Chemical Analysis, 5th Edition. New York: W.H.
Freman and Company, 1999.Grolier. 1996. Ithaca, NY: GeoSystems Global Corporation, CD-ROMKarow, Julia. 2000.
Stoppling Prions from Going Mad. Scientific American. Karp, Gerald. 1999. Cell and Molecular Biology: Concepts and Experiments 2nd ed., New York.
John Wiley & Sons, Inc.Prusiner, S. B. 1995. The prion disease.
Scientifique American. 271:77-83. (Oct.)Prusiner, S.
B. 1997. Prion disease and the BSE crisis. Science 278: 245-251Purves, William K., Orians, Gordon H., Heller, Craig.
1998. Life, the science of biology5th ed, Salt Lake City. Sinauer Associates.