Notes: Pyruvate Oxidation & Krebs Cycle

Pyruvate Oxidation

·With the presence of oxygen, pyruvate will enter the mitochondrial matrix to be further broken down before the Krebs cycle, this process is called the pyruvate oxidation.

  Steps

1. Decarboxylation - one carbon atom and two oxygen atoms are released as a carbon dioxide molecule
2. Oxidation - the remaining 2-carbon fragment is oxidized to form an acetate ion. NAD+ is reduced to become NADH
3. Attachment- the acetyl group of the acetyl ion is attached to a sulfur-based compound, Coenzyme A, to form Acetyl-CoA (2C), which is the end product of the pyruvate oxidation.  

Note: step 2 and 3 are coupled reactions 

Krebs Cycle

· Each acetyl-CoA enters a cyclic metabolic pathway, called Krebs cycle, that generates NADH, FADH2, and ATP. 

 Steps

1. Acetyl-CoA(2C) enters the Krebs cycle to react with oxaloacetate(4C) to form citrate(6C). During the process, CoA is removed. 
2. Citrate undergoes isomerization to become isocitrate(6C)
3. Isocitrate undergoes decarboxylation to be alpha-ketoglutarate (5C). Meanwhile, NAD+ is reduced to be NADH.
4. -Alpha-ketoglutarate undergoes decarboxylation again, NAD+ is reduced, and CoA is added. 
    - product:　succinyl-CoA (4C)
5. - Substrate phosphorylation. A phosphate group replaces the CoA in succinyl-CoA, and binds to a GDP to form a GTP. Then the terminal phosphate of GTP is transferred to a ADP to form a ATP. 
　- product: succinate (4C)
6. Succinate becomes fumarate(4C). Another electron carrier, FAD is reduced to become FADH2.
7. Fumarate reacts with water to become malate(4C)
8. - Malate is oxidized to become oxaloacetate (4C)
    - NAD+ is reduced to be NADH
9. Oxaloacetate will continue to react with acetyl-CoA

Note: 

- for each acetyl-CoA that enters the cycle, 3 NADH, 1 FADH2 and 1ATP is produced.
- Notice the carbon atoms from the original glucose molecule have been removed as CO2 by the end of step 4 (alpha-ketoglutarate → succinyl-CoA)

***Found a diagram that's numbered with steps and is somewhat corresponding to what I wrote above (step 1 is pyruvate oxidation). Also note that the substrate phosphorylation of ATP is not labeled from step 5 to 6, and water is not added into the fumarate from step 7 to 8. 

Reflection: "Details of Being Human"

 To eat more meat or more vegetables, has been a ceaseless debate between the vegetarians and the meat eaters. This article provides deeper insights and a new perspective to this topic. 
  Based on the article, I think people should decrease the  intake of red meat and also eat more vegetables. Humans lack a type of sialic acid, Neu5Gc, which is present in animal. The human immune antibodies will attack the acid if it is present in human body. It is evident from the reactions of Dr. Varki's patient after being injected horse serum. Dr. Varki and his colleagues found out that the antibodies will attack the acid when a person consumes much red meat, which is rich in Neu5Gc, such as lamb and beef.  And this leads to many human-specific diseases that are associated with chronic inflammation, including heart disease and cancer. On the other hand, white meat, which is not high in Neu5Gc and also rich in protein, seems very ideal for human. Therefore, humans should eat more white meat and less red meat. Additionally, protein is vital for humans and cannot be gained by only eating vegetables. 
  Eating more vegetables is essential to one's wellness. Eating vegetables can prevent constipation; constipation can cause the accumulation of toxins in our body. Plant cells contain cell walls, which are primarily composed of cellulose. Cellulose cannot be digested because humans lack the enzyme that breaks the beta-glycosidic bonds in it, so it has to be excreted from the body. The cellulose stimulates the corresponding receptors on the rectum, and cause the egestion of the feces. Also vegetables are low in calories and cholesterol and they will the decrease the risks of getting heart diseases. Furthermore, vegetables provide vital vitamins and minerals for human body.  
Vegetables might provide some amino acids, but not all 20. It is true that the essential amino acids can be replenished by artificially synthesized tablet. However, this method is fairly new, and no documented long-term risks or side-effects is available. Therefore, humans still need to eat meat. 
  In conclusion, humans should eat more meat than vegetables and more white meat than red meat. 
  The loss of Neu5Gc should be considered beneficial overall, despite some of the side effects.  The loss of Neu5Gc makes us more susceptible to some diseases such as, rheumatoid arthritis, bronchial asthma.  Additionally our hearing abilities and healing rate is decreased. However, back to million years ago, the loss of the sialic acid made us thrive, speciate and differ from other mammals. Because the presence of Neu5Gc will cause the susceptibilities to chimpanzee malaria disease. After this long time, we have become highly intelligent specialized mammal that is at the top of food chain. That must have a great connection with the loss of Neu5Gc, although we have not found out why. 
  The three million dollars used by CARTA was not wasted because it made a lot of great discoveries possible, despite the fact that it has not found the ancestors of humans. Because of CARTA, we now know the probable reason for humans to speciate, being immune to some chimpanzee malaria disease P. reichenowi that is why we lack Neu5Gc and have Neu5Ac. This finding can lead to research related to the unique physiological changes that Neu5Ac can bring. 
  

Reflection: "SARS - What Have We Learned?"

  Media definitely should become more open and fast in informing the public with any outbreak of diseases. One of the main purposes of media is to share information. People nowadays are becoming more and more dependent on the new technologies that are speedily emerging.  Through these devices, people can know what has happened on the other side of the world. This is a good sign because it allows us to know the important things, such as the outbreak of diseases. If the media is not open but very secretive about them, people's health will be put into probable risks. By knowing the facts, people can take precaution on their own to minimize the damage.  For example, during the outbreak of SARS, Chinese health authorities have failed both to tackle its spread and to provide sufficient information to their counterparts in other countries about what is going on. This causes the wide spread of the disease. It even affects many countries across the ocean, such as the United States and Canada. In addition, the daily life of the majority of the Chinese citizens is significantly affected (especially the south). Speaking of my own experience, I was in the Southern China during the outbreak. I could vaguely recall that it was after quite a few cases had been found, the associated public health institutions started to take action to raise people's awareness. It might be a little late to control. Furthermore, the public health care institutions were not specific about what to do, so the public started to panic. The citizens did everything they could to be sanitized and reduce the chance of being affected. On the streets, almost everyone was wearing a surgical mask. Vinegar (claimed to have sanitizing effect) was always sold out in the supermarket. However, the truth was that SARS could only be spread by close contact with the patients instead of airborne particles, Therefore, the media should be more open and up-to-date about the spreading of any diseases. 

  If a country is withholding the information about the spreading of disease from the public, the WHO, along with other countries  should take action to pressure the government. There are a few possible ways to do that. First, people could start a parade around the embassy of that country. All the trade activities that present a probability should be forbidden. And everyone from that country is prohibited to enter. Also, the associated health organizations in the country should start to tell any information they know to the local communities, at the same time, they can speak up  for the public so that everyone could have access to the important information.  Furthermore, other countries can send doctors and scientists to the affected country to collect data and facts to inform the locals. In short, pressuring the government, taking action by the local associated health organizations and sending doctors and scientists to the country, is the three ways to cope with the situation where a country withholds information about the outbreak of disease from public. 

Reflection: Dissection of a Fetal Pig

This dissection was finished in two days.

Day 1: Lower body (intestines, stomach, liver, pancreas, kidney, renal arteries)

After obtaining all the necessary equipment, we started the dissection.

Before we cut open the pig, we needed to determine the sex of the fetal pig. We could not find any opening near the umbilical cord, so we thought it might be female. However we thought there was a possibility that if this specimen was male, its opening near the umbilical cord could be undeveloped yet, since it was so small compared to the specimen other groups had.

Then we started to cut the skin of the abdominal area. We found out that there was a fat layer between the skin and the internal organs. This proved that lipids were great protection.  

Finally we cut open the abdomen of the pig. There was a lot of grayish liquid pouring out. It could not have been blood since it must have been drained out already. It might be substances that preserved the specimen.

I was surprised to see that the liver was so large in terms of the size. It looked like it was 3 times larger than the intestines. Then I remembered that this was a fetal pig, which meant there wasn't anything in its intestines, so the intestines were flat and small in size. Additionally, we saw two red blood vessels at the lower abdominal cavity. We inferred they were renal arteries, and they were dyed red for students to see better.

Removal of the organs. We needed to be very careful in order not to damage other organs. 

Outcomes of day 1! We had isolated liver, stomach, pancreas,kidneys, small and large intestines. 

The pancreas was not easy to find. It was a leaflet-like structure that was close to the stomach, and was easy to be damaged.

Day 2: Upper body (Lungs, heart, thyroid, brain)

After 1 day, the specimen had become very dehydrated. We started to open its upper body. The first organs exposed were the lungs.The heart was hidden between the lungs. After removing the lungs and the heart, we tried to locate the thyroid glands, which should have been near to the trachea. However, we were not sure if we had found it, or some adipose tissue. 

Moving up to the brain. Since the specimen was very undeveloped, its skull was not bone yet but cartilage, which was quite soft but strong enough to hold the brain within. Due to its fragility, we cannot use scissors or knife. Instead, we used a very sharp needle-like tool to gently divide the head into four areas (the white lines on the head in the photos below), then we used small tweezers to open up its skull. The process took a lot of time and required concentration and refined movement.  

After that, we tried to isolate the brain and the brain stem attached. We cut open the spine at the back of the head a bit.

Like all the other groups, we had failed to isolate the brain stem attaching to the brain.

Out of curiosity, we wanted to know what the brain felt like, and we all touched it. The result was that it felt like jelly.

That was the end of the of this dissection. Here is an overview of all the organs we isolated.

Photo Creds to Nicole Hong

Reflection: "Scanning Psychopaths"

 The court should consider assigning a heavier sentence to the psychopaths.  The law is to enforce the order of the society. The sentence should be based on the seriousness of the crime and if the criminal has understood the wrongdoing in their behavior.  According to the article, the psychopathic people show lack of empathy. Lacking empathy makes the psychopaths have a higher tendency of committing serious crime because that will make them make them forget the law - not to hurt others. And that explains why 1/5 of the serious crimes are committed by the psychopaths. In short, psychopathic criminal should be given a heavier sentence because it's hard for them to understanding they are doing wrong, and heavier sentence might help them. Add to that, I think the court should not released the psychopathic criminal back to society again, and they should be permanently kept in some form of treatment institution. 
  Although a lot of people who commit serious crimes such as murders are psychopaths, it is still not appropriate to label all of them serial killer because not all of them will be one. From the article, the "psychopathness" is assessed by a tool called PCL-R in four different aspects: "interpersonal", "affective", "lifestyle" and "anti-social." Each experimenter is given a score out of 40. The higher the score, the higher the "psychopathness."  A criminal who has a sore of 35, claims that he would never be a serial killer. And he thinkst his high score is "a talent, not a sickness - [he] can make good strong decisions, and it's good to have some distance with people." Additionally, a experimenter mentioned in the article says that he agrees to do the experiment on empathy simply because he likes Meffert, the person who carries out the experiment, and he says "if they say the study can help people, it's good."
  Speaking of video games, which is very common among young people nowadays, might diminish the ability to feel empathetic towards others because the environment has a great impact on people's behavior and mindset.  Just like love, empathy is not inborn but acquired through learning, despite the fact that this learning has been done early in one's life. Babies don't appreciate their mothers and fathers' hard work and effort. They cry and only care about themselves. Afterwards, babies gradually understand their parents, and learn how to love and care for other people just like what their parents have done to them. When they fall down, their parents will go and help them get up and console them. When they are sick, their parents will take them to the hospital or stay at home to take care of them. Indeed, we learn to be empathetic and caring in the process like this from parental care(environment). Also, parents and teachers teach us the moral principles in life, what is good and what is wrong, which is also an example of how environment affects us. On the other, the violent video games, act as the opposite environment, they will definitely change the way players think and feel in someway, and empathy will be decreased.

Reflection: “While You Were Sleeping”

  Staying  up all night is definitely not an efficient way to study. Although from the length of the studying time, it seems that students can learn more materials. However, there is some importance of sleep that cannot be neglected. First, it provides an opportunity to repair and develop, and it also "re-energized" your body. Students stay up all night will absolutely feel tired and difficult to concentrate on studying the following day, which decreases the efficiency of studying. Additionally, according to the article, during the slow-wave sleep, the neurons start to enhance the connections between them about the information learned during the day, which strengthens the procedural learning. Experiment shows that the volunteers who have just learned new things right before they go to sleep show better performance after they wake up. 
  Schools should not start 1 hour later to "let students have better sleep," because it is ineffective. When I was in China, students needed to get up about 6 AM because the class started at 7. There were quite a few people who were sleepy. After I came to Canada, the school started at 9, and there were still students who slept over(being late), or felt sleepy. This proves that there is no correlation between the time schools start and the quality of sleep the students have. Another perfect example is that, in Canada, there is a time change between summer and winter. This year, on November 3, at 2 AM, the clocks were turned backward to 1 AM. Theoretically, if it true that the quality of students' sleep can be benefited from school starting 1 hour late, there should be a noticeable change in the students. They should be more energetic, more concentrated in class due to the improved sleep. However, there is not. Those who have been energetic all the time are still energetic;those who have been constantly sleepy before still repeatedly inform me their tiredness. In conclusion, the quality of sleep the students cannot be improved by school starting 1 hour late, but only by better time management and self regulation. 
  I am positive for inserting an hour for nap after lunch to increase students' academic performance. After lunch, the blood flows into the stomach and intestines to aid digestion. Students won't be as concentrated the first class, which is approximately 0.5 hour after they finish their lunch, due to lack of blood in the brain(this is even worse for the students if they have a test after lunch). After 2.5 hours' morning classes, I strongly feel that we need more time to rest. Besides, many clubs and other activities during lunch time, which shortens our resting time even more. In China, the gap between the last class in the morning and the first class in the afternoon is 2 hours. I used to wake up fresh and sober after a "power nap" and can understand, respond to the teacher quickly. In conclusion, schools should add an extra hour into the lunch time, so that the students can rest well and do better in the afternoon classes.

  

Reflection: "What's in the Medicine Cabinet?"

  Essential workers in my opinion are health-care workers and the scientists who develop the new drugs. Physicians and nurses would face an overwhelming number of patients per day during a pandemic. They are the ones who can help. The amount of doctors is very low in Canada, about 1.9 physician/1000 people. If they get sick, who is going to treat the sick? The health care system of the country will be paralyzed, and the impact of the pandemic will be more significant. The scientists who develop the drugs should get the early treatments, too. They should be protected from the disease so that they could continue to discover new, more effective drugs that can cure people. Also, they taking the drugs would be a way to show the public that the drug is trustworthy—the people who come up with it even dare to consume it. Besides that, it could also ensure that the quantity of the drugs. Scientists themselves have to take the drugs before giving them to the public. 
  We should have amantadine and rimantadine as back-ups although they have unwanted side effects. By interfering with the viral protein M2, amantadine and rimantadine can as effectively as neuraminidase inhibitors. Plus, they are a lot cheaper than the neuraminidase inhibitors. They can somewhat suppress the pandemic. Every drug has side effects, it is unreasonable for drugs to be stopped using because of them, especially under such special conditions. The pharmaceutical companies should warn their costumers about the negative effects in advance, so it's up to the costumers to decide.  However, government should not spend a lot money on amantadine and rimantadine, they can only be used as back-ups.
  We should invest more money into stock piling than developing new drugs. Tamiflu is the best of the four currently available anti-in fluenza drugs. Also, the effects of the virus on the populations are unknown: which age group is most likely to ill, how fast is the virus would spread and how ill would people get. If there is no enough drugs, we have to prioritize the treatment groups, which can lead to ethical controversies because everyone has same right, why can one person get the protection over another because of their identity? However, if we have ample amount of drugs, this would not happen. Everyone will then could have the chance to be protected from the flu. If we spend a lot of money on developing new drugs, supposedly they are developed successfully and better than the previous, the population will still suffer because it's all too late to produce enough for everyone. For those reasons, the WHO is strongly supportive about stockpiling drugs as well. They have been using all its persuasive power to get the government place the orders now.
  

Reflection: "Brain Craze"

  People should spend some time on video games, but not the majority of time. There are some benefits from video games. They can make people think and respond quickly; they keep people interested and entertained. Also, according to the article "Brain Craze," the video game introduced by the Japanese neuroscientist Ryuta Kawashima can  increase the prefrontal cortex, and it is said to be a booster for people's mental capabilities, especially for the elderly. However, there are also a lot of disadvantages of video games. First, they will decrease people's attention span. When people are accustomed to the short, attention-grabbing scenarios in the games, they will find a hard time concentrating on things that require long-term attention, such as reading. In addition, for this article, the credibility of the video games created by Kawashima for improving mental capabilities is still questionable. A lot of scientists still think  that the reason why the scores for the game can be improved over time, is because people get better at the device itself rather than actually improving mental health. In my opinion, this so called "brain age" game for training brain is merely a fad. The scores only show how well the user has learned the skill to play the game. Like playing a new sport and driving a car, if you have mastered certain techniques, along with a lot of practice, you can do well. Besides the lack of evidence to show that the video game can actually improve mental health, I'm amused by how the game gives a number to indicate brain age. It is as irrational as some Facebook app such as "To Test Your Mental Age." How do they know what a 62-year-old brain is capable to do? How do they know a 20-year-old brain can answer this many questions correctly? This video game can be absolutely be replaced by the traditional and effective way: reading and doing mathematics. In conclusion, people can spend some time playing video games only for entertainment, but should not heavily rely on them.  
  Neuroscience should be considered as an emerging area of medicine, and be given more attention and done more research on it. The nervous system is the commander of all the organ systems in the body. If we understand it better, we might find the cure for many mental diseases such as Alzheimer, schizophrenia. Also, we might know how to use our neurons maximally, instead of the less than 10% for now, so that everyone can be smarter. Add to that, it's probable to extend people's life expectancy by knowing a way to prolong the vitality of the neurons.  

Reflection: “Deaf by Design”&“Sound and Fury”

    The deaf absolutely have the same right to abort a hearing fetus as the hearing people have rights to abort a deaf fetus. Hearing parents do not like the idea of having a deaf baby because they are going to have trouble communicating with their children, and it pains the parents to see their children being isolated. On the other hand, the deaf parents also have frustrations if they have a hearing child, because they can't guide their children in the hearing world when they can't hear any sound. Also, the deaf parents would have the fear of  
their children feeling embarrassed by them someday because they can't hear, speak and seem so uneducated and...silly. Both hearing and deaf parents have very understandable reasons. Then if the hearing people can abort a deaf fetus, why can't the deaf people abort a hearing fetus? Doesn't every citizen have the same rights?
    The term "disability" is relative; it all depends on the environment. The deafness is a kind of variation caused by the mutations in the genes for proteins connexin  26 and connexin 30, according to the article Deaf and Design. Under the current environment, "deafness" not a favorable trait due to the inability to hear and respond to sound, and therefore causes difficulties in communication and isolation from the majority of hearing people. Hence, the hearing people would call the deaf people disabled. However, deafness could be a selective advantage if the environment changes. If someday, all of a sudden, there is no sound in the world anymore, the hearing people will sink into the isolation of not being able to communicate, but the deaf people will still can communicate with each other by sign language. Then, the hearing people will be considered to be "disabled." There are many other examples in the nature, too. For instance, in a forest where the seeds are hard and formidable, the birds with small beaks will be considered to be "disabled" compared to the birds with big beaks, because they can't open the seeds. However, if it's in another environment - a forest with seeds that are much easier to be open, having small beaks is then not a disability. 
    Altering the genetic codes seems very positive for me, because then we could cure a lot of genetic disorders, such as cystic fibrosis, Huntington's chorea. These mutations are harmful, so they are self-limiting. If these harmful alleles will eventually decrease and die out of the population, why we can't we just stop them right away artificially? Also, in this case, deafness can be prevented by altering the genetic codes.
    In my opinion, it is not in Heather's best interest to be raised as the only hearing child in the family, the reason is that it is not good for her to develop the speech. It takes a lot of time and practice to master a new language. Heather can't improve her speaking skill very fast if she keeps using sign language all the time to the other family members. If her siblings also get cochlear implant, they can practice speaking with each other.