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!
Sunday, October 30, 2011
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.
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.
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.
Wednesday, October 19, 2011
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.
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.
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.
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.
Saturday, October 8, 2011
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:
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:
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| 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! |
Thursday, October 6, 2011
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!
Wednesday, October 5, 2011
Nobel Prize Winners 2011 - Physiology or Medicine
2011 Nobel Prize in Physiology or Medicine
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| 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.
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.
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