Useful Materials for Chapter 12

The video above explains the role of transcription factors in transcription. This helped me understand how transcription factors can help in gene regulation. It is a brief video with interesting animations that allow you to visualize the process. Please excuse the strange music; it seems the majority of bio videos online have some form of strange music on them.

This next video is on ribosomes and how they work in translation. I found this interesting because it shows the assembly of the ribosome, which occurs after encountering the mRNA in the cytoplasm. The video also explains the initiation factors that are involved in ribosomal activity, as I described in my previous post.

As always, I recommend Khan Academy videos if you are having difficulty understanding the concepts presented in the chapter. This video takes you back to DNA structure, then walks you through transcription and translation.

Translation: DNA to mRNA to Protein

Translation occurs using ribosomes, which are present in the cytosol of eukaryotic cells. mRNA of eukaryotic cells has to leave the nucleus and move to the cytoplasm for translation to occur. In prokaryotic cells, ribosomes are capable of attaching to the mRNA while it is still being translated from DNA.This is possible since the translation begins at the 5' end of the mRNA and transcription produces mRNA in a 5' to 3' direction, so the 5' end is created first. Since transcription and translation are done simultaneously, mRNA is more short-lived compared to that of eukaryotes. The multiple steps involved with the translation of mRNA in eukaryotic cells allow for greater ability to regulate protein production.

Ribosomes are composed of two subunits, a large one and a small one, that assemble at the mRNA and otherwise exist separately in the cytoplasm. The ribosomes contain proteins, ribosomal RNA (rRNA), and transfer RNA (tRNA). tRNA are adaptor molecules with a 3' end and an anticodon. The anticodon reads the triplet codon of the mRNA using complementary base pairing and the 3' end is attached to a particular amino acid. rRNA catalyzes the addition of amino acids to the growing protein.

There is an area of the mRNA near the 5' end that is not translated, and is known as the UTR or untranslated region. The UTR is located between the first nucleotide and the start codon of the mRNA strand. The UTR is important to translation because it provides a binding site for the ribosome. The human mRNA UTR is typically about 170 nucleotides long. Translation begins after a complex is formed on the mRNA strand. First, three initiation factor proteins bind to the smaller ribosomal subunit, after which this complex along with a tRNA that contains methionine bind to the mRNA that is being translated, close to the AUG start codon. While methionine is the first amino acid of all new proteins, it can be removed after translation. The second amino acid on the protein influences whether or not an enzyme removes the initial methionine. For example, if the amino acid alanine is the second amino acid, then the initial methionine is removed by an enzme. If the second amino acid is lysine, then the methionine is not removed.

The initiation factors are removed from the initiation complex on the mRNA when the large ribosomal subunit binds to the complex. This subunit contains three sites that the tRNA can bind to: an A site, an E site, and a P site. The mRNA codon and the aminoacyl-tRNA anticodon pair up at the A site to ensure that the correct amino acid is added to the polypeptide. The P site is where the amino acid on the 3' end of the tRNA is transferred to the polypeptide chain. The E site is where the "empty" tRNA stays before it is released into the cytoplasm. Only a tRNA containing methionine is able to bind to the ribosome's P site while the second mRNA codon lines up at the A site.

The ribosome moves along the mRNA in a 5' to 3' direction and covalently binds amino acids to one another, producing a polypeptide. This process requires GTP as an energy source and elongation factors. When the tRNA-amino acid complex binds to the A site, GTP is cleaved to form GDP and is released with certain elongation factors and is later recycled by other elongation factors. Peptidyl transferase activity binds the first and second amino acids together. This is a catayltic function of rRNA, although this process was originally thought to have been catalyzed by enzymes. Once the bond is formed, the ribosome shifts so that the now-empty tRNA molecule is in the E site. The tRNA is then released by the ribosome into the cytoplasm, where it picks up another amino acid to repeat the process. The A site is also empty for the next tRNA molecule that corresponds to the next codon. The protein-coding sequence of mRNA ends with UAA, UAG, and UGA. tRNAs do not recognize these codons and another protein, called a release factor, binds to it and causes the polypeptide to be removed from the ribosome and the ribosome disassociates.

Silencing Genes to Prevent Infection

Electron Micrograph of Ebola Virus Particles

Ebola is a virus that causes a deadly hemorrhagic fever and is spread through contact with blood and contaminated needles. About 85 percent of the reported human cases of Ebola have resulted in death. The use of vaccines has protected monkeys, but are only effective when given prior to exposure to the virus. A team of scientists, including Thomas Gesibert, was initially attempting to boost host immunity for people exposed to the virus, but later turned to muting the virus's genes. This would at least buy time for other treatments, including the vaccine, to start working.


Gene silencing, or RNA interference (RNAi) occurs naturally. Some portions of DNA are transcribed into RNA, which are then translated into proteins that keep our cells functioning. However, there are other stretches of DNA that are transcribed into siRNA, or small interfering RNA, that is not translated into proteins. Instead of being translated into protein, these RNA strands are bound to portions of other RNA strands that have complementary sequences. This prevents the RNA from being translated into proteins and offers greater control over gene expression. Geisbert and his team attempted to artificially replicate this process to work on Ebola by creating siRNA that would bind to polymerase L, a gene that is vital for replication to occur.


The researchers were able to silence the gene and prevent replication effectively in cell culture studies, but encountered a new problem when testing the approach on animals infected with Ebola. "Naked" siRNA in blood and body tissues is broken done by enzymes. When the synthetic siRNA was injected into the test animals, the researchers needed to develop a "vehicle" that the infected cells would take up so that the siRNA contained within it would not be broken down by enzymes. The initial packaging system was ineffective, but Geiser then packaged the siRNA into SNALPs, or stable nucleic acid lipid particles. Cells like dendritic cells and macrophages are targeted by Ebola and were capable of taking up the SNALPs, resulting in a successful test with siRNA-containing SNALPs when used on guinea pigs.


When testing the approach on monkeys infected with Ebola, Geiser also included siRNAs to target viral genes that are thought to inhibit the immune system. They injected the SNALPs containing the siRNAs into the monkeys 30 minutes after injecting Ebola and injected the SNALPs every day for a week as well. After seven days, all of the monkeys were virus-free. Gesier hopes to push his approach to work on people infected by Ebola up to 24 hours after infection.


To access the article that I got my information from, click here.

Useful Materials for Chapter 11

The video above reviews the process of how DNA is packaged, how it replicates, and the various proteins and enzymes involved in the process. I found this to be really interesting because it looked less cartoon-ish than biology videos tend to be. It also goes more into topics that we had not focused on in this chapter, such as DNA transcription into RNA. If you are looking for a more detailed version of what we have learned in class, I suggest looking at the lecture I have posted below. I recommend this video particularly for people who have not grasped the basics that are necessary for truly understanding DNA replication. These basics include the structure of the nucleotides in DNA and how this relates to the process of replication. It also goes into more detail about the roles of the various enzymes involved in DNA replication.

There are several parts to this lecture that can all be found on youtube.

Telomerase Structure, Function, and Biogenesis

Telomerase is an enzyme, more specifically a reverse transcriptase, that adds telomeres to the ends of DNA. Telomeres is the end of a eukaryotic chromosome, consisting of a short nucleotide segment that repeats from a few dozen times to several hundred times. They basically make up for the inability of DNA polymerase to fully replicate the 3' linear chromosome ends. Telomerase consists of two parts, TERT (catalytic telomerase reverse transcriptase) and TR (telomerase RNA), and functions as a ribonucleoprotein. There have also been several accessory proteins that have been identified that function in the regulation, biogenesis, and localization of the enzyme. Understanding telomerase's molecular mechanisms is essential to developing therapies for disorders and cancers that are related to telomerase.


Idiopathic pulmonary fibrosis, or IPF, is the most common type of telomere-related disease. Mutations in hTERT and hTR genes are the cause of the defect. These mutations can lead to extra-pulmonary complications that result from telomere shortening. These complications include bone marrow failure. There is also evidence that points towards IPF being a manifestation of telomere syndromes that were autosomal dominant. With each generation, it evolved from pulmonary fibrosis to disorder that is predominantly related to bone-marrow failure. The article goes on to explain the the significance in defects of telomere for understanding the disease patterns, pathophysiology, and genetics of idiopathic pulmonary fibrosis. 


To see the articles that I got my information from click here and here.

The Value of "Junk" DNA

The genetic blueprint of human beings consists of 23 linear chromosomes that contain 3.42 billion nucleotides. The genetic blueprints of most mammals consist of similarly significant amounts of nucleotides. Some extremes in nucleotide numbers do occur in mammals, such as the red vischaca rat (8.21 billion nucleotides) and the bent-winged bat (1.69 billion nucleotides). Regardless of what kind of animal, there is a large excess of DNA that does not code for proteins. Approximately 2% of DNA codes for proteins in humans. For several decades, scientists were confounded by the purpose of such "junk" DNA, which often consisted of repeating segments that are dispersed throughout the genome.


These repeating segments come about when sections of DNA move within the genome to different positions. This process is called transposition. Biologists now believe that these transposable segments are not useless, but instead provide greater ability for the organism to evolve. They serve as areas for genetic recombination and provide new signals for genetic expression. Genomes are dynamic, with certain elements becoming extinct as new elements appear. Functional DNA can therefore be created from "junk" DNA. The term "exaptation" is used when describing how genetic entities can change their role, despite their original role if they had one at all. For example, biologist Gill Bejarano discovered a DNA fragment that was exapted as an enhancer, increasing gene transcription, when it had originally inserted itself anywhere into the genome.


DNA sequences that are nonfunctional in certain organisms could be functional in others, becoming an exon that is transcribed to messenger RNA. While non-functional DNA can be seen as "junk" DNA they actually do actually have a role in the genome. These segments are important to evolution. To access the article that I retrieved my information from, click here.

Useful Materials for Chapter 9

Click here to see a useful animation on signal amplification. It explains how signal transduction pathways, while they may seem unnecessarily complex, amplify a cell's response to a single signal molecule. If each signal only caused a reaction in one particular protein, for example, this would not be a very effective response. This animation uses the hormone epinephrine as an example. Although it only activates a single molecule of adenylyl cyclase, the cellular response is amplified through the pathway. I suggest keeping an eye on amplification count on the right of the screen while moving through the animation.

This video walks you through the fight-or-flight response of the body. I found it useful for making a real-life connection involving the three-stage process of the cells' response to signal molecules. It also included some extra information on the role of nerve signals in the process. I enjoyed the graphics in this video, as they zoomed in and out of the cells and display exactly how the response takes place.

Also, if you are looking for an online flashcard site, I suggest studyblue.com. It's really simple to use and I may share some flashcards that I create on there in the future.

Cancer-Causing Bacteria Induces Apoptosis

Barry Marshall discovered that stomach ulcers are caused by bacteria after he drank a petri-dish containing Helicobacter pylori, a bacteria. He subsequently developed gastritis as a result, then cleared this through the use of antibiotics. The discovery that stomach ulcers could be treated with antibiotics was significant for the medical community as they could lead to stomach cancer and duodenal ulcers.

Helicobacter pylori Micrograph

Researchers have recently identified a bacterial toxin, called vacuolating cytotoxin A or VacA, that plays a role in apoptosis. Apoptosis is a process of programmed cell death. VacA had previously been shown to cause cell death, which is important to the development of gastric cancers. Instead of attacking the cells lining the stomach, Helicobacter pylori causes the cells to undergo apoptosis. Too little or too much apoptosis can lead to several conditions, such as neurodegenerative diseases, cancers, and autoimmune disorders. Apoptosis can occur naturally for several reasons such as well cell population needs to be regulated or as a defense mechanism. Cell death can also be induced due to damage in the cell caused by disease or noxious substances.


VacA is a product of Helicobacter pylori. In order apoptosis to occur, the mitochondria are targeted by VacA, since these parts of the cell are responsible for energy production. VacA makes the outer membrane of the mitochondria permeable,disrupting its electron gradient. This electron gradient is needed for oxidative phosphorylation during cellular respiration. Thus, the mitochondria is unable to produce adequate amounts of usable energy for the cell. In addition, VacA disrupts the structure of mitochondria by preventing them from forming a network and effectively isolating them. Since having functioning mitochondria is essential to cell life, the VacA results in the cell killing itself through apoptosis. Through these mechanisms, Helicobacter pylori causes cell death of stomach cells in small areas, which can then results in gastric cancer and, in less severe cases, peptic ulcers.


Click here to access the article on the cancer-causing bacteria and here to access the article that I got my general information on apoptosis from.

Drug Discovery Opportunities through Allosteric Modulators of G Protein-Coupled Receptors

This article is about the new opportunities for drugs to be discovered through the identification of allosteric ligands. These have generally not been the main focus of GPCR, or G-Protein Couple Receptors. GPCR are located in cell membrane surfaces and respond to a variety of extracellular signaling. They have been investigated for the discovery of several drugs that moderate specific GPCRs. When GPCRs are stimulated by the proper ligand, intracellular signal transduction is initiated. Activation of  β-arrestin pathways and activation of G-proteins are the two mechanisms of signal transduction. The binding of the lingand stabilizes the receptor, allowing it's C-terminal domain to interact with protein complex and its Gα portion to hydrolyse GTP and interact with adenylate cyclase and/or phospholipase C. The receptor is phosphorylated when it reacts with G-protein-coupled receptor kinases and is able to bind β-arrestins. This prevents more G-protein signaling from occurring and also begins a series of intracellular events that are independent from G-proteins.

GPCRs have been pharmacological targets. However, only certain classes of GPCRs are able to be targeted with drugs. The article is proposing that idenitfying allosteric ligands that bind to different sites other than the orthosteric site will provide new opportunities for drugs to be produced. Allosteric modulators allow for enhanced saturability as well as selectivity. Because they cause conformational changes in their receptors, allosteric modulators can alter affinity and capability. Therfore, allosteric modulators can impact how receptors relate and respond to their binding partners, producing selective responses. The article then describes different techniques that can be used to identify allosteric modulators.

For more information, click here to access the article that I got my information from.

Useful Materials for Chapter 7

So cellular respiration can seem complicated, but I have found that animations can help you to understand the various steps of it. You can click here to get a very quick visual of the entire process. I liked this animation because it gives you a quick idea of how the energy intermediates as well as waste products are produced. I also like how it keeps track of the carbon molecules of the glucose. However, I also wanted to look at something that was more detailed. Click here for a link to a much more detailed cellular respiration animation. This one kept track of all the energy intermediates produced during the various steps, counting them up as the animation proceeds. It didn't confuse me with all the names of the complexes in the electron transport chain. Instead, it just labeled them "Complex I", "Complex 2", and so on, also indicating how the electrons move due to how strong an electron acceptor each complex was. There is another part aftewards that includes all the names of the complexes in the chain, if you wish to know them. There are also several "pop-up questions" that test your understanding of the material presented in the animation.

Once you think you know respiration pretty well, you can click here to take a self-test! I know, I know, tests in school are enough, but this could help prepare you for the rapidly approaching bio exam, so why not? This test was useful because it is graded online, which can help you target which topics you may need to study more. You should try this link as well, and click on "begin problem set" on the bottom of the page. It includes helpful tutorials for questions that you don't know the answers to. Not all the questions pertain to this chapter, so just skip those. With that, have fun studying!

Salmonella Uses Human Intestines to Foster Growth

The bacteria Salmonella enterica, which is a common cause of food poisoning, takes advantage of the body's immune response to enhance its production of energy. Bacteria have to produce energy in order to survive, either by respiration or fermentation. However, oxygen is sparse in human intestines, so bacteria use fermentation in order to survive. Respiration is much more energy efficient than fermentation is, producing a higher number of ATP.

When Salmonella is injested, it invades the intestine's surface, causing the immune system to produce oxygen radicals that kill of the bacteria. Some bacteria are killed by this process, but many others benefit from a sulfur compound that the oxygen radicals create. This sulfur compound is called tetrathionate, which Salmonella can use instead of oxygen to carry out respiration. As we learned in class, oxygen is needed to act as the final electron recpetor in the elctron transport chain. Tetrathionate acts as the final electron acceptor for Salmonella, which is what allows it to produce energy through respiration rather than the less energetically productive process of fermentation. Tetrathionate had previously been by researchers to promote Salmonella growth in samples, but it was throught that this sulfur compound was not found in living human beings. Stimulating the immune response gives Salmonella an advantage, as it allows them to carry out respiration and thus produce more energy than the other bacteria in the intestine. When this response is stimulated, it also allows Salmonella to spread to other hosts, as the body induces diarrhea and vomiting in an attempt to rid itself of this bacteria.

The symptoms of Salmonella infection include vomiting, fever, abdominal cramps, and diarrhea. While most people recover quickly, it can be fatal in people with suppressed immune systems. Antibiotic treatment is ineffective, as it also ihibits the growth of beneficial bacteria in the body. Researchers are hopeful that targeting sulfur compounds will help stop the bacteria from establishing itself in the intestine.

You can click here for the article that I got my information from or you can click here for a shorter article that basically talks about the same thing.

Approved Drugs that Shift Cellular Energy Metabolism toward Glycolysis Identified

This article discusses the discovery of several drugs that affect cellular energy metabolism in animals. Changes in energy production pathways in cells can occur naturally, such as in development or in response to energetically demanding activities, but can also occur due to disease. The goal of the team that discovered these drugs was to identify compounds that can induce this shift in a safe manner, and research how the therapeutic value of this shift. Cancer cells produce energy predominantly through glycolysis, so a mechanism that would switch energy production from this may suppress tumor growth.

Previous studies show that mitochondrial respiration could mimic ischemic preconditioning. This is when there is a brief decrease in blood supply to a tissue, which can protect it from future damage if blood supplies are completely cut off. A new screening strategy was created by the team, in which there were two environments: one that had glucose (glycolysis and respiration), and another that had galactose (respiration). A drug that would be able to redirect metabolism from respiration to glycolysis would would stop the growth of cells in the galactose while it would have minimal effect on the cells in the glucose. Several drugs were identified to cause a shift in energy metabolism, including anticancer drugs that inhibit rapidly proliferating cell growth.

Most drugs that mimic ischemic preconditioning are too toxic for human cells, but the researchers were able to identify eight drugs that produced a less intense, but significant, shift from respiration to glycolysis. One of these drugs was meclizine, which is an over-the-counter drug that is used for treating nausea and vertigo. This drug was tested on and it was discovered that pretreatment with meclizine reduced ischemic damage in cardiac cell in the case of a heart attack. It also reduced damage to brain cells when tested on a stroke model. A lot of testing is still needed before this type of drug can be used on human cases.

Click here to see the article that I got my information from.

Autophagy: Finding the Line Between Normal and Diseased

Autophagy is when a cell gets rid of intracellular components, such as organelles and proteins. The inability of autophagosomes to do work can lead to several diseases, including cancer, inflammatory diseases, and neurodegeneration. Autophagosomes are membrane-bound organelles that transport cellular components to lysosomes, fusing to become autolysosomes. Enzymes in the autolysosome then degrade the enveloped material, converting it to basic materials that can be reused in the cell.

As more research has been conducted on autophagy, it has been observed that there are several links between autophagy and human diseases. Some autophagic proteins, such as beclin-1, have tumor suppressing properties. Mice that lack the Beclin-1autophagy protein have shown more formation of tumors than those who have Beclin-1. Mutations in the genes of autophagosomes can lead to the accumulation of damaged DNA as well as genome instability. Observing autophagic pathways can be tricky because it can be difficult to distinguish them from normal pathways.

Autophagosomes are biologically important molecules because they function in homeostatic processes. These homeostatic mechanisms include helping the cell signal its homeostatic condition to the outside environment and modifying the cell's metabolic state to more effectively counter harmful external stimuli. Their activity is regulated by external conditions, such as nutrients and stress, and mTOR, which supervises cell signaling pathways involved in cellular metabolism. Researchers are looking to determine what function autophagosomes have on developmental processes in the hopes of producing disease therapies through their research. For more information, click here to access my article.

Enzyme Inhibitor That May Slow Cancer Growth

Enzyme Inhibitor That May Slow Cancer Growth Developed by U of I Scientist
This article talks about research on an enzyme inhibitor that affects an enzyme called betaine-homocysteine-S-methyltransferase (BHMT). BHMT catalyzes a reaction that results in the production of methionine from homocysteine. Methionine is an amino acid that is essential for many biological processes, and cancer cells require high levels of this amino acid. Tim Garrow, who researched this topic, says that the ability to lower methionine levels in the body could allow us to selectively inhibit cancer growth. Garrow first became interested in BHMT when he realized that high levels of homocysteine lead to several diseases, such as thrombosis. 


By studying BHMT's crystal structure, Garrow was able to design inhibitors for it. These inhibitors were injected into the abdomens of mice, and results showed that this caused them to have increased homocysteine levels. This shows that the inhibitors did prevent the enzyme from catalyzing the homocysteine to methionine reaction. Garrow also stated that using the BHMT inhibitor alongside another cancer drug could cause the other drug to have a greater impact, as the availability of methionine to the cancer cells is decreased.


However, elevated homocysteine levels can also have a negative impact on the body, such as leading to vascular diseases. Garrow claims that the BHMT inhibitor would most likely be used for short periods of time, while vascular diseases take a long time to develop. There is also another potential use for BHMT inhibitors. One of the substrates of BHMT is betaine, which donates a methyl group to homocysteine to form methionine. Betaine also functions in regulating cells' water content, so BHMT inhibitors might be useful in preventing unwanted water loss in the body. This article shows an interesting application of man-made enzyme inhibitors for the purpose of slowing cancer growth.

Useful Materials for Chapter 6

Click here for a link to an enzyme animation. It allows you to mess around with the various factors that can impact the rate at which reactants become products. It is a rather simplified animation, as you can't choose between noncompetitive inhibition or competitive inhibition and such. However, you can change the number of enzymes, substrates, and inhibitors that you choose to be present. You can then see how long it takes for all the substrates to become enzymes. Enzymes are shown in green, substrates are blue, products are red, and inhibitors are yellow. You can grasp the basic concepts of enzyme functioning rates and inhibition using this. For example, you could choose for there to be only one enzyme, 10 substrates, and and 20 inhibitors in your setup. It would take a long time for a significant number of products to be formed. Next, you could raise the number of substrates to 60 and notice that although the inhibitors do slow down the product formation rate, it is overcome by the sheer number of substrates present.


If you are having a tough time understanding the thermodynamics of metabolism, I suggest you click here. It's just an article, and I know articles are boring! But this is written by a chemistry professor and she does a pretty good job of explaining endergonic reactions, exergonic reactions, coupling of reactions, and whatnot. So, if the book is just not doing it for you, check this article out. If for nothing else, then do it because she included this picture (see below) in her article.

FoldIt!

So, FoldIt is a program that allows you to fold proteins. As you fold the protein, you get a score based on how well it is folded. Your goal is to reach a pre-determined score and then you get to move on to the next puzzle. So....

Puzzle 3-1 is called "Sheets Together"

Basically all I had to do with this was wiggle the protein by clicking the "Wiggle All" button. This created hydrogen bonds in the protein (the blue and white ones), which stabilized the protein. Doing this made the protein properly folded and allowed me to get the score I needed to move on.

Puzzle 3-2 is called "Lonely Sheets"

For this one, I had to match up the sheets and so I couldn't just use the "Wiggle All" button, but also had to drag the sheets to one another. I did this by hitting the shift key, clicking on the sheet, and dragging it. Then, I wiggled the protein because that allows the rubber bands to pull together. I put rubber bands across the areas of the puzzle where the protein sheets were too far apart. These were identified by red balls between the parts that were too far apart. I actually managed to finish this puzzle using only one rubber band. However, I had to reset the puzzle a couple of times before I was able to do this! At the end it looked like this:

The rubber band I used is shown in purple.

Puzzle 3-3 is called "Sheets and Ladders"

I managed to solve this puzzle using only one rubber band as well. I used the same method, making the rubber band and then hitting "wiggle". It immediately got me the points I needed, which was kind of surprising. I noticed that at the end there was still space between it, shown by the red ball, but I decided not to argue it. Hydrogen bonds were formed in the process. As usual, the rubber band is in purple and the hydrogen bonds are blue and white. Here is the completed puzzle:

I did puzzles 3-4 and 3-5 as well to get to puzzle 4-1. 3-4 or "Lock and Lower" introduced the concept of freezing a portion of the protein so that it doesn't move while the protein was wiggling. After freezing part of the protein, I was able to solve the puzzle using just one rubber band and then wiggling, which resulted in several hydrogen bonds that stabilized the protein.

I solved 3-4 or "Rebuild" by right clicking on a portion of the protein that seemed unstable and clicking rebuild. After I stopped the rebuilding, I clicked wiggle, which allowed some stabilizing hydrogen bonds to form.

Puzzle 4-1 was called "Hide the Hydrophobic"

Orange sidechains were hydrophobic and wanted to be buried inside the protein. If there was a yellow bubble around an orange sidechain, it signified that the sidecain was being exposed, and was not hidden in the middle of the protein. Blue sidechains needed space, and had to point outwards. Solving this puzzle was very simple. I just clicked and dragged the orange section to the middle (no pressing shift!) and then I clicked and dragged the blue sidechain so that it pointed outwards. I was able to finish this puzzle in two simple steps, with no wiggling, rebuilding, or rubber banding involved!

Basic Fold It Tips: If you are having trouble with the folding the first time you try, walk away from the computer. The first time I did this I wanted to chuck my computer against a wall. I suggest you don't do this unless it's your sibling's computer. Also, you can always undo a step or go back to the original settings. This helps a lot when you are first starting out. I found myself making a huge mess with the proteins, and undoing was the only way to get myself out of it. So, with that, have fun with your protein folding!

Glycosylation

Similarities and Differences in the Glycosylation Mechanisms in Prokaryotes and Eukaryotes

Glycosylation of proteins occurs in both prokaryotic and eukaryotic cells. More than 70% of eukaryotic proteome is said to be glycosylated. While the percent of proteins that are glycosylated in prokaryotes is unknown, it is a common occurrence. The article presents four major glycosylation pathways that are present in archaea, eukarya, and bacteria, which vary in their abundance depending on what kinds of organism is being presented. For example, N-glycosylation, mediated by oligosaccharyltransferase, is fairly abundant in archae and eukaryea, but not in bacteria.


N-glycosylation starts with the formation of sugars in the cytoplasm, which assembles into a oligosaccharide precursor that is attached through pyrophosphate to a lipid carrier. Once the oligosaccharide is assembled, the lipid-linked oligosaccharide (LLO) is flipped, and faces the ER's lumen. The oligosaccharide is then moved from to the acceptor protein from the lipid carrier. This step, in which the LLO is attached to an asparagine amino acid is catalysed by an enzyme.


The other major type of glycosylation is called O-glycosylation, which also occurs in a systematic fashion. It begins when the linking monosaccharide is attached to serine or threonine, which are acceptors. Sugars are subsequently added one at a time to form a mature glycan. Most O-glycosylation events occur in the Golgi apparatus, although there are some that occur in the endoplasmic reticulum as well. There is a tremendous variety of sequences that can be attached, causing there to be much diversity in O-glycosylation.


All glycoproteins in eukaryotes go through substantial remodeling in the Golgi apparatus upon exiting the endoplasmic reticulum. There is no equivalent to the Golgi apparatus in prokaryotes, so glycoproteins there do not undergo remodeling. The article goes on to describe how the different types of glycosylation differ in the different domains. For a more in-depth explanation, feel free to check out the link for my article that I posted above!

Nobel Prize Winners 2011 - Physiology or Medicine

2011 Nobel Prize in Physiology or Medicine

Nobel medicine prize honors work on body's defenses

Bruce Beutler (middle) with colleagues in the lab
http://www.nobelprize.org/nobel_prizes/medicine/laureates/2011/beutler-photo.html 

This year, the Nobel Prize in Physiology or Medicine went to Bruce Beutler, Jules Hoffman, and Ralph Steinman. Beutler and Hoffman researched innate immunity, the non-specific initial response to foreign microorganisms that starts inflammation. Steinman investigated the role of dendritic cells in adaptive immunity, which is a specialized response to foreign microorganisms that occurs after the initial, non-specific response. Adaptive immunity results in the production of antibodies and killer cells that attack infected cells.  After the initial response to a certain pathogen, we develop a resistance to it for future exposures due to adaptive immunity. 


This has allowed for improvement in vaccines as well as a better understanding in stimulating the immune response to cancer. Their research has led to the development of a new kind of "therapeutic vaccines" that can cause the immune system to fight tumors. This new information can also help researchers who are attempting to figure out a way to lessen the response of the immune system when it exhibits excessive enthusiasm, resulting in too much autoimmunity and inflammation. This is the case with autoimmune inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, and type 1 diabetes. Research on dendritic cells has led to the launch of the first ever therapeutic cancer vaccine, which treats advanced prostate cancer.

Wee for a Wii

Strange but True: Drinking Too Much Water Can Kill

This article talks about a 28-year-old woman in a water-drinking contest in order to win a Wii. She drank 6 liters of water in the time span of 3 hours and died after going home due to "water intoxication". Over-drinking of water causes hyponatremia, or dilution of the blood, which results from drinking too much water. It is when the sodium concentration of the blood drops to below 135 millimoles per liter, or 0.4 ounces per gallon. Severe hyponatremia can can cause nausea, fatigue, headaches, and mental disorientation.

The kidneys control the amounts of water and solutes that are retained in the body or leave the body. When too much water is consumed in a short period of time, the kidneys are incapable of flushing all of it out, and so the blood becomes waterlogged, or saturated with water. The water is drawn to areas where solute concentrations are higher, so it leaves the blood and enters the cells. Most cells have room to stretch and accommodate the water, as they are embedded in tissues such as muscle and fat. However, nuerons do not have this kind of room to stretch. Brain cells are tightly packed in the skull and cannot expand to accommodate the excess water. So, severe hyponatremia that occurs in a short amount of time can lead to detrimental brain swelling that can result in severe medical conditions including seizures, coma, respiratory arrest, herniation of the brain stem (click here to find out when brain stem herniation is), and death.

In the majority of cases, water poisoning occurs due to a combination of excessive water drinking and an increase in the production of antidiuretic hormone (ADH). This hormone instructs the kidneys to retain more water in the body. More of this hormone is secreted at times of physical stress, such as when running a marathon, despite the consumption of extra water to compensate for water loss.

Useful Materials for Chapter 4

Cell Structure Animation
This animation helps review the various cell parts in prokaryotic cells, eukaryotic cells, animal cells, and plant cells. If found it useful for remembering the various functions of the parts that we had learned in biology before. You can click on the different parts for more information and there is a short quiz at the end that will help you to recognize whether or not you should review some more.


Virtual Cell Animations
This is a link to a free app that you can download on your iPod touch/iPhone/iPad. It includes animations on topics such as photosynthesis and cell transport. Unfortunately, I was unable to download it. So, if you do let me know what it's like! There is also another free one called 3D Cell Simulation and Stain Tool. Here is a screenshot: 

Tay-Sachs Disease

Tay-Sachs is an autosomal-recessive genetic disorder for which there is no treatment or cure. It is caused by a lack of an enzyme called Hex-A, or hexosaminidase A. This enzyme is necessary for the break down of fatty wastes in the brain's nerve cells. When there is an absence of this enzyme, the fatty waste substance (GM2 ganglioside) builds up in the cells, causing damage to the nervous system to point at which the individual with Tay-Sachs dies. The Tay-Sachs causing gene is found on chromosome 15. Tay-Sachs is an inherited disease, for which anyone can be a carrier. About 1 out of every 250 people in the population are carriers for Tay-Sachs. If both parents of a child are carriers, there is a 25% chance that the child will be born with Tay-Sachs. Certain populations, such as French Canadians and Ashkenazi Jews, appear to have increased risk of being carriers of Tay-Sachs.

There are three forms of Tay-Sachs: infantile, juvenile, and late onset. Only one of the forms can be present within one family. The most common form is classic infantile Tay-Sachs, for which symptoms develop around 6 months of age, causing the affected individual to die by the age of 5. The symptoms involve a slowing down of development, as mental and motor capabilities decrease. Eventually, the child becomes unresponsive to their environment. This disease is diagnosed either by a blood test to check the child's Hex-A levels or by identifying a cherry-red spot on the child's retina, which is classic for infantile Tay-Sachs.


For more information look at these articles that I referenced: http://www.ntsad.org/index.php/tay-sachs
http://www.tay-sachs.org/taysachs_disease.php

Endocrine Reviews: Defective Protein Folding

Beyond the Signal Sequence: Protein Routing in Health and Disease
This article focuses on the various diseases that originate from improper protein folding. The intracellular routing for many proteins is controlled by a sensitive QC, quality control, system. This system recognizes structural proteins as well as destroys defective molecules. Abnormal proteins are capable of interfering with normal cell function and can lead to cell death. Diseases that are caused by abnormal proteins usually involve the inability of a protein, or protein complex, to carry out its normal function or when a protein is incorrectly folded. Another cause is when proteins are not properly positioned within a cell.
One disease that results from improper protein folding is nephrogenic diabetes insipidus (NDI). This disease can either be inherited or acquired. The kidneys are unable to concentrate urine, even if there are normal levels of the antidiuretic hormone vasopressin present in the plasma. Vasopressin aids the body by regulating water loss and retention, by reabsoprtion of water from urine and by fusing vesicles that hold aquaporin-2 (AQP2) water channels. This prevents an increase in the water permeability within the ducts.  NDI can be caused if there are mutations in the vasopressin type 2 receptor (V2R) gene or in the AQP2 gene. The X-linked version of NDI is caused by mutations to the VR2 gene while the more rare, non-X linked version is caused by mutations to the AQP2 gene.
In VR2 mutations, more than 90% were unable to perform effective intracellular transport due to improper folding. There may also be an accumulation of VR2 in the ER. In AQP2 mutations, proteins are incapable of proper trafficking, causing the protein to remain in the ER. One type of mutation in the AQP2 has resulted in an inherited NDI that is autosomal-dominant.

Chapter 3: The Chemical Basis of Life (Macromolecules)

Valine

Alanine

Proteins

There are different types of proteins with various functions. These include (but are not limited to!): motility, receptor, membrane transport, enzyme, and catalyst proteins.
Amino acids are held together by peptide bonds caused by dehydration reactions. Amino acids can be polar, nonpolar, acidic, or basic. For example, glycine and proline are non polar, and glutamate is acidic. The structure of protein determines its function
There are four levels of proteins structure:
Primary Structure: This is the sequence of amino acids. Protein does not stay in a linear state due to the combination of hydrophobic and hydrophilic amino acids it contains, as the hydrophilic ones are "happy" by water while the hydrophobic ones are not. So, hydrophobic ones are protected while hydrophilic ones are exposed.
Secondary Structure: Amino acids interact with neighboring amino acids, forming hydrogen bonds, to bend and twist the protein chain. Some have distinctive shapes, causing them to be named (alpha helix or beta strand). The shape is stabilized by hydrogen bonds using "local folding" as specific parts of the chain can fold.

Alpha Helix

Beta Strand

Tertiary Structure: This is the overall three-dimensional shape of the protein. Non-polar (hydrophobic) parts are on the inside and polar (hydrophobic) on the outside. Ionic bonds (such as between acids and bases) as well as hydrogen bonds help to stabilize. R-groups are what determine stability.
All proteins exhibit primary, secondary, and tertiary structure. Folded proteins are functional but they can denature and become inactive or unfolded. Denaturation can occur due to an increase, in heat, pH, or salt levels.
Quaternary Structure: This is when two or more proteins chains join together in a complex protein. This level of strucutre may or may not be present in a protein.
Proteins often have non-protein components, such as the heme group in hemoglobin. This group is an iron-containing group to bind gases such as oxygen.


Nucleic Acids
Nucleic acids are polymers of building blocks called nucleotides. The two types of nucleic acids are DNA (deoxyribnucleic acid) and RNA (ribonucleic acid). DNA stores hereditary information, including all information for proper cell function. RNA helps in assembling proteins. Nucleotides are composed of a 5-carbon sugar, 3 phosphate groups, and a nitrogenous base. 4 carbons of the sugar are part of the ring while the 5th is branched from the ring. All nucleotides have a 3' hydroxyl group and the phosphates are linked at the 5' carbon. The nitrogenous base is linked at the 1' carbon. In a DNA nucleotide, the 2' carbon has simply a hydrogen while a RNA nucleotide has a hydroxyl group at the 2' carbon.
A nucleoside consists only of the sugar and nitrogenous base. A nucleoside with one phosphate group is called a nucleoside monophosphate. If it has two phosphate groups it is a nucleoside diphopshate, and if it has three phosphate groups it is a nucleoside triphosphate.
There are 4 nucleotides used to construct DNA and 4 to construct RNA. The nucleotides of DNA are adenine (A), thymine (T), cytosine (C), and guanine (G). The nucleotides of RNA are adenine (A), uracil (U), cytosine (C), and guanine (G). They differ in their nitrogenous bases. There are two basic groups of nitrogenous bases: purines and pyrmidines. Purines consist of two rings while pyrimidines have only one ring. 

The polar functional groups in the nitrogenous bases result in hydrogen bonds forming, which is what creates the double helix structure of DNA. The two strands are antiparallel, linked by phosphodiester bonds, which are covalent bonds specifically found in nucleic acids. This type of bond is analogous to a peptide bond in proteins. Nucleotides are linked to the next using a dehydration reaction. A and T bind while C and G bind in DNA. In RNA, A binds with U and C binds with G. A sugar-phosphate backbone is created that gives the skeleton for the molecule. DNA has opposite ends, called 5' and 3' ends, based off of which side of a sugar is facing what end.

Due to the double-stranded nature of DNA, the nucleotide sequence of one sequence is complementary to the other chain.
Differences between RNA and DNA:

• RNA has ribose sugars, DNA has deoxyribose sugars
• RNA exists as single strands, DNA has a double-helix structure
• Uracil replaces thymine in RNA
• RNA is synthesized from a DNA template
• At the 2' carbon, there is a hydroxyl group attached in RNA but only a hydrogen atom in DNA

DNA Double-Helix

Helpful Links

Click here for a link to a site that helps you remember the functional groups as well as learn to identify them. I especially liked the "U-Draw Functional Groups" animation. It basically gives you different molecules. You can draw on it and circle the functional groups. Then, you can hit "check" to see if you were able to find them all.

This video explains purines and pyrimidines. It made the structures clear and explain why and how they bind.


Article
http://www.ncbi.nlm.nih.gov/pubmed/21928440
This article pertains to this chapter because it is discussing a protein that may have anti-cancer, anti-HIV, and hemolytic properties. It is unknown whether this depends on the lipid-bilayer of cell membranes or the chiral receptors. A test was done using the enantiomer of the protein, which resulted in the exclusion of a chiral reception, indicating that the phospholipid bilayer is what has an impact on the effectiveness on this drug. This plays into macromolecules, as it includes both proteins as well as lipids (of the cell membranes).