Amazing Enzymes!

https://en.wikipedia.org/wiki/Anselme_Payen

In 1833, the first enzyme was discovered in its concentrated form by a French chemist with the name of Anselme Payan (1). Payan discovered diastase, otherwise known as amylase, which is a starch-breaking enzyme in our saliva and pancreatic fluid and allows starch to be fully digested (2). What is an enzyme? Enzymes will alter a molecule in a specific way and are responsible for the speed, or rate, of a chemical reaction (3). Enzymes are essential for humans because they help with digestion, DNA replication, etc. In the digestive system, enzymes help break down large molecules into smaller ones so that we can digest that substance much easier and absorb the necessary nutrients (3). During DNA replication, the enzymes help to unwind the DNA strands and get them copied (3). What is an enzyme made of? An enzyme is a complicated, ribbon-like structure that is made up of one or more folded proteins.

https://www.medicalnewstoday.com/articles/319704.php

To the left is an image of the enzyme diastase. As you can see, it is basically a glob of different string/ribbon-like objects, but this is only one way to view a protein. In this secondary structure, there are what is known as a beta sheet and alpha helix. A beta sheet, which appears to be the red ribbon on the image to the left is defined as being a wave-like structure. It is linked together by hydrogen bonding and it "allows for more hydrogen bonding by stretching the polypeptide chain" (8). The alpha helix is defined as being a spiral or coiled structure like the dark yellow ribbon right next to the red beta sheet. This structure is formed when the polypeptide chain twists, allowing the amino acids in the center to form hydrogen bonds with one another, ultimately creating a very strong helical structure (8). Overall, this image accentuates the secondary structure while a protein can be in a variety of different structures, such as in primary, secondary, tertiary, or a quaternary form that vary in appearance to the one I have provided. The image below shows a more accurate representation of all the different forms of proteins that can be found and also includes a close up on the alpha helix and beta sheet I described earlier.

https://en.wikipedia.org/wiki/Protein_folding

An enzyme also contains what is known as an active site, which is a region on the enzyme that binds to a substrate, which is a reactant molecule. When the substrate binds to the enzyme, specifically onto the active site, an enzyme/ substrate complex is formed. Once the complex has formed, the enzyme will slightly change its shape to create an enzyme/ product complex in which the new product will form (4). As you can see in this gif below, the enzyme's active site is designed to connect to only specifically shaped substrates. 

            https://gfycat.com/gifs/search/enzyme

Another way that people associate an enzyme with a substrate is from the idea of a "lock-and-key (3)." The "lock-and-key" model was first proposed in 1894, which basically sounds like its name, where only one type of substrate can fit into the enzyme's active site. Now, we use what is called the induced fit model, which builds off of the "lock-and-key" model. The induced fit model reveals that once the substrate has connected to the enzyme, the active site will slightly adjust its shape as it interacts with the substrate and will then conclude with the catalyst beginning (3). So why are they so important? Enzymes are important because they help keep the major processes in our bodies going at the rate that is required for our survival (5). Imagine if our bodies could not break down large molecules into the small, nutritious form that our bodies require. Besides diastase, what is an example of another enzyme?  Another example of an enzyme that is actively working in our bodies is called telomerase. Telomerase is an enzyme that can "extend the length of telomeres on a chromosome" and  can also "make DNA from an RNA template (6)."

https://gfycat.com/gifs/search/telomeres

The green structure that is moving above is the telomerase at work. As you can see, the telomerase adds a complementary strand (the letters/bases in red) from the RNA strand, making the telomere longer. The length of the telomere is important because as the chromosome replicates, the end bases (at this point it is the telomere) fall off, and if all the telomeres are gone then the important parts of the DNA sequence will start to fall off (7). If DNA is lost, that can either mean one of two things: no effect or something really bad. Sometimes if a DNA sequence is missing there can be no effect on the end goal, but other times it can be the reason why we have certain diseases, like cancer. Overall, enzymes are very important for the essential processes in our bodies to run at the rate necessary for our survival.

Just remember...

https://gfycat.com/evilmealybirdofparadise

References: 

1)   This website gives a brief description of the life of the French chemist Anselme Payan. The editors of Encyclopedia Britannica. Anselme Payen. Encyclopedia Britannica. https://www.britannica.com/biography/Anselme-Payen. Updated January 2, 2019. Accessed February 23, 2019. 

2)   This website gives a brief description of the enzyme Diastase, and I also used the dictionary definition of amylase. Diastase. Enzyme Education Institute. https://enzymeeducationinstitute.com/enzymes/diastase/. Accessed February 23, 2019. 

3)   This website gives a thorough description of what enzymes are and what specific functions. Newman, T. Enzymes: How they work and what they do. Medical News Today. https://www.medicalnewstoday.com/articles/319704.php. Updated January 11, 2018. 

4)   This website also talks about what enzymes are and their function, but also touch on the specifics, such as what an active site, substrate, cofactors, and environmental factors are. Enzymes and the active site. Khan Academy. https://www.khanacademy.org/science/biology/energy-and-enzymes/introduction-to-enzymes/a/enzymes-and-the-active-site. Accessed February 24, 2019. 

5)   This site briefly describes why are enzymes are essential for survival. Who am I?. Science museum. http://whoami.sciencemuseum.org.uk/whoami/findoutmore/yourbody/whatdoyourcellsdo/whatisacellmadeof/whyareenzymesimportant. Accessed February 24, 2019. 

6)   This website gives information about the function and relationship between telomeres and telomerase. Telomeres and telomerase. Khan Academy. https://www.khanacademy.org/science/biology/dna-as-the-genetic-material/dna-replication/a/telomeres-telomerase. Accessed February 24, 2019. 

7)   This website gives information about telomerase and its function. Telomerase. Biology Dictionary. https://biologydictionary.net/telomerase/. Published in 2018. Accessed February 24, 2019. 
8) This website gives a brief description of the alpha helix and beta sheet in the secondary structure of a protein. Chapter Two: Organic Chemistry. The Virtual Cell Webpage. https://www.ibiblio.org/virtualcell/textbook/chapter2/ps1.htm.  Accessed March 3. 

Model Organisms

        In modern society, we have things known as clinical trials. A clinical trial is a research program that is conducted with patients to see if a new drug, treatment, or device is safe for humans (1). The patients, however, are not the first test subjects to use these new drugs, treatments, or devices. The very first test subjects are known as model organisms, which are basically a smaller and more affordable representation (or model) of a human.

https://piergen564s18.weebly.com/model-organisms.html

These subjects must meet all of the requirements necessary to participate in a specific research study. What does that mean? Scientists would not use a killer whale to determine how our cells grow and divide. They would strategically choose a test subject that has a similar biology to ours or a similar genetic makeup (2). Rather than using a random animal, scientists would use Saccharomyces cerevisiae (otherwise known as yeast) to study how human cells divide (2). These organisms allow scientists to have a better understanding of how our bodies will react to certain drugs or determine how certain parts of our bodies work. Who could possibly be a better representation of a human, than a human? The issue with using humans as primary test subjects is that it is simply unethical to do so. In order to test a disease, one must become infected with the disease first in order for the scientist to even consider what direction to go in so that he or she can find the cure. In other words, the scientist needs to study the disease and its behavior in the body, then decide where the disease is targeting, and then determine what is the best mode of treatment to not do more harm than good. Also, model organisms are generally easier to control when it comes to their breeding patterns, allowing for a large number of test subjects when needed and inexpensive sources when supplies run low. But how is using these organisms any more ethical? In a perfect world, everyone's questions would be answered and every disease would have a cure already created but unfortunately, that is not the case. Scientists still have to figure out all the answers to the "why" and "how" within our biological systems, and they need something to try and solve those types of puzzles with. On the bright side, the organisms used for such research are protected under the “NIH’s Office of Laboratory Animal Welfare (OLAW),” which are “laws, regulations, and policies to ensure the smallest possible number of subjects and the greatest commitment to their welfare (3).” Furthermore, every scientist is required to provide a justification for what kind of animal(s) will be used, how many are needed, how each will be used, describe how they will be housed and cared for, and how veterinary care will be provided to them (3). Ultimately, the organisms used in these `studies are protected and monitored by the NIH to ensure their safety and wellbeing. So what kind of organisms are used for these kinds of studies? Here are some examples (2):

         Saccharomyces cerevisiae:

https://www.researchgate.net/figure/Scanning-electron-microscopy-image-of-Saccharomyces-cerevisiae-The-budding-yeast-cells_fig1_308144762

Saccharomyces cerevisiae (9), also known as Yeast, has been used to understand how genes become involved with certain diseases, based on whether or not they are activated or not (for more on gene expression go to my previous post!). It has also been used to understand the cell cycle. Yeast has allowed scientists to understand how a cell will divide and duplicate itself, which has led to beneficial discoveries, like what we know this far about cancer. Cancer is the abnormal growth of cells, therefore, understanding the cell cycle and how cells grow is crucial if we ever plan to find a cure for cancer. Humans and yeast only share the same domain of Eukarya (8 &9). According to the NCBI, "a typical laboratory yeast strains produce 20-30 daughter cells per mother and one lifespan experiment requires 2-3 weeks (11)." Based on this information, we can see how fast an average Yeast reproduces. This is convenient for researchers who need a lot more time, than a Yeast's typical lifespan, to conduct their research or study. Here is a database that has been curated from over 2,000 publications about the pathways and genomes for the Saccharomyces cerevisiae S288c, https://yeast.biocyc.org. 

Drosophila melanogaster:

https://www.researchgate.net/figure/Scanning-electron-microscopy-image-of-Saccharomyces-cerevisiae-The-budding-yeast-cells_fig1_308144762

Drosophila melanogaster, also known as a fruit fly, has led to a broadened understanding of how fertilized eggs develop into complex organisms…otherwise known as babies…or you (10)! Fruit flies have also been associated in discoveries with the circadian rhythms, which are the “physical, mental, and behavioral changes that follow a daily cycle (4).” This is the explanation for why organisms generally sleep when it is dark and are awake when the sun is up. This research was able to connect certain circumstances like “sleep deprivation, obesity, diabetes, depression, and other human health conditions (2).” Fruit flies and humans are both in the Domain Eukarya and Kingdom Animalia, but branch off at the Phylum. Fruit flies are in the Phylum Arthropod, while humans are in Chordata (8 &10). Although the lifespan of a fruit fly is determined by the temperature, the typical lifespan of a fruit fly is about 40-50 days and in that time they can lay "several batches of eggs (12)." These are just a few reasons as to why fruit flies are such a vital model organism for biomedical research. The database provided, https://nucleus.iaea.org/sites/naipc/twd/Pages/Databases.aspx, contains different research publications involiving fruit flies.

  

Mus musculus:

https://biox.stanford.edu/highlight/toenail-trim-saves-lab-mice-common-life-threatening-skin-condition

Mus musculus (otherwise known as a laboratory mouse) is  considered to be one of the most common biomedical model organisms to ever be used (6). They have been used in drug testings for decades. The research conducted on this rodent has led us to understand “what we know about cancer-causing molecules (2).” Mice have contributed to the creation of Lyrica (for Fibromyalgia or Epilepsy), Lantus (for types 1 and 2 diabetes), Zetia (for high cholesterol), and so many more (5). The cause for their use is because their bodies react to certain drugs and diseases just as ours would. Both mice and humans can be found in the Kingdom Animalia, Phylum Chordata, and  Class Mammalia. The difference in taxonomy between humans and mice begins at the Order; mice are in the Order Rodentia, while humans are in Primates (7&8). The lifespan of a lab mouse (in a protected environment) can be approximately 24 months (13). These organisms clearly have a longer lifespan than fruit flies and yeast, making them valuable for longer research assignments. This database, https://www.labome.com/method/Laboratory-Mice-and-Rats.html, gives an overview of how mice (and rats) are involved in biomedical research  from a variety of different sources. 

In order for a drug to be approved, it must undergo animal and eventual human testing. The U.S. Food and Drug Administration requires that a drug is tested on animals before it can be used in clinical trials with humans (5). More than likely you or a loved one has taken a drug or had a vaccine that was used in animal testing and you just did not know it. Model organisms are very important because they allow us the ability to fight against harmful diseases, stay healthy, and discover new things about our biology that we would never have known before!  

http://dev.biologists.org/content/141/21/4042

References:

1)   This site reveals what a clinical trial is and the process that the patients will encounter if/when they participate in one. Clinical Trials: A Guide for Patients. WebMD. https://www.webmd.com/a-to-z-guides/clincial-trial-guide-patients#1. Updated October 28, 2017. Accessed February 14, 2019. 

2)   This site provides many examples of model organisms, as well as describe what an organism is and what it takes to become one. Using Research Organisms to Study Health and Disease. National Institute of General Medical Sciences (NIGMS). https://www.nigms.nih.gov/Education/Pages/modelorg_factsheet.aspx. Updated October 2017. Accessed February 15, 2019. 

3)   This website describes the NIH’s (National Institutes of Health) mission to ensure the welfare of those animals being used in research and also describes what they do to ensure that their mission is fulfilled. How does the NIH ensure animal welfare?. National Institutes of Health. https://grants.nih.gov/grants/policy/air/NIH_ensure_welfare.htm. Updated April 9, 2018. Accessed February 15, 2019. 

4)   This gives a thorough understanding of what the circadian rhythms are and how it connects with day to day occurrences like sleeping or being jet lag. Circadian Rhythms. National Institute of General Medical Sciences. https://www.nigms.nih.gov/education/pages/Factsheet_CircadianRhythms.asp. Updated August 2017. Accessed February 16, 2019. 

5)   This site provides a brief summary of the importance of animal testing and a list of the top 25 drugs that had been tested on animals. Animals Behind Top Drugs. Foundation for Biomedical Research. https://fbresearch.org/medical-advances/animal-testing-research-achievements/animal-research-behind-top-drugs/. Copyright 2016-2019. Accessed February 16, 2019. 

6) A database that provides information about laboratory mice and their involvement in biomedical research. SMI. An Introduction to the Laboratory Mouse : Mus musculus.  Soceity of Mucosal Immunology.  http://www.socmucimm.org/1038/. Published June 3, 2014. Accessed February 19, 2019. 

This site provides cool facts, along with the scientific naming of different animals. I searched each individual organism from this site to find information on their taxonomy. 

7) Mouse. A-Z animals. https://a-z-animals.com/animals/mouse/. Updated September 10, 2018.  Accessed February 19, 2019. 

8) Humans. A-Z animals. https://a-z-animals.com/animals/human/. Updated September 10, 2018. Accessed February 19, 2019.  

9) This site provides that information into each of the classification levels of Yeast. Baker's and Brewer's Yeast. Bioweb. http://bioweb.uwlax.edu/bio203/s2012/vandenla_beth/classification.htm. Accessed February 20, 2019. 

10) This site gives plenty of detail about fruit flies, from other types of flies to the life and habits of fruit flies. Fruit Flies. Bugwoodwiki. https://wiki.bugwood.org/HPIPM:Fruit_Flies. Updated January 27, 2010. Accessed February 20, 2019. 

11) This online journal gives a detailed description of of the life span of a budding Yeast. Measuring Replicative Life Span in the Budding Yeast. NCBI. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797481/. Published June 25, 2009. Accessed February 21, 2019. 

12) This website gives a brief summary of the life span and cycle of a fruit fly. Life Span & Life Cycle of Fruit Fly. Orkin. https://www.orkin.com/flies/fruit-fly/life-span-of-fruit-fly. Accessed February 21, 2019. 
  
13) This blog post gives descriptive reasoning as to how to determine when a mouse is considered old (while comparing mouse years to humans) and also gives their maximum lifespan. Hagan, C. When are mice considered too old?. Jax. https://www.jax.org/news-and-insights/jax-blog/2017/november/when-are-mice-considered-old. Accessed February 22, 2019. 

The Central Dogma and Gene Expression

The cells within us make decisions all the time that we are not aware of. Throughout our lives, our cells can select what kind of protein will or will not be created. These decisions are what make our blood cells with hemoglobin (which helps transport oxygen around the body and bring carbon dioxide to the lungs to be exhaled), brain cells, muscle cells and basically anything essential to life. They also decide the non-essential things like directing the production of hair cells and hair color. So how do cells do this? This is all thanks to the central dogma, which is within the process known as gene expression. The central dogma is when a DNA strand turns into a single RNA strand and then into a protein (1).

https://genius.com/Biology-genius-the-central-dogma-annotated

From the image above, one can see that DNA can be replicated multiple times and will eventually undergo an expression called transcription. Transcription is the process "in which RNA polymerase uses one strand of DNA as a template to synthesize a complementary RNA sequence"((2) p.G:24), basically meaning that an enzyme creates an RNA strand from DNA. The newly formed RNA strand can then undergo the second expression, which is known as translation. Translation is when a nucleotide directs the amino acids to form a protein ((2) p.G:24). 

http://www.dbriers.com/tutorials/2012/12/tip-to-remember-difference-between-translation-vs-transcription/

The image on the right reveals that transcription is basically transcribing a message, where you take one set of information (DNA) and rewrite the same information (RNA) to get a better understanding. The next form of expression is translation, where the RNA strand will become a protein. The image above on the left reveals that translation is like translating one language (RNA) to another that is different yet more ideal (new protein). The central dogma is important because it gives scientists a broader understanding of how genetic information is interpreted and regulated within our cells. Why should we care? 99.9% of all human DNA is the same (4). Its arranged the same and in the same order, so the question is why do some people get diseases and syndromes that others do not? That is why we should care. Not everyone's genes are expressed the same way, which is why scientists continue to do research on gene regulation. So what exactly is a gene and what does it mean that it is "expressed?" A gene is a segment of DNA that instructs the RNA strand to make a certain protein ((2) p.G:10). Gene expression is when a cell selects which proteins or RNA molecules are to be made through transcription and translation ((2) p. 262). This process is the reason why some of us have brown, red, blonde, or black hair. Gene expression is the overall name of the process, while the central dogma is each of its individual steps. Gene expression is important because it's why we have such things like brain and red blood cells. Even though each of those cells come from the same DNA sequence, they have completely different structures and functions.

https://www.livescience.com/62756-blood-cells-morph-into-neurons.html

https://www.asianscientist.com/2017/11/in-the-lab/red-blood-cell-maturation-proteomics/

The discovers associated with gene expression have led scientists to understand more about "cancer, autoimmunity, neurological disorders, diabetes, cardiovascular disease, and obesity" (3), which have all been linked to having a gene expression malfunction. How can there be a malfunction with an individual's gene expression? Generally, these types of diseases and syndromes are likely to occur when an individual's regulatory region, transcription factors, cofactors, chromatin, regulators, and/or noncoding RNAs have a mutation (3). Two examples include cardiovascular disease and diabetes. A congenital birth defect can give an individual cardiovascular disease because of a misregulation when the cardiovascular system was being created. Normally when our blood sugar level drops, the pancreas will decrease the amount of insulin being produced and will release cells that are known as glucagon. These glucagon cells make the liver turn glycogen (polysaccharide; complex sugar) back into glucose (simple sugar) so that our blood sugar level can increase and get back to normal (5). In an individual with diabetes, there can be a mutation in the “pancreatic master transcription factors and the sequences they bind” are associated with diabetes. In another scenario, the cells can have its transcription factors, like “HNF1α, HNF1β, HNF4α, PDX1, and NeuroD1,” be mutated which causes the cells to not be able to properly respond to the insulin that is produced (3). Any of these transcriptional factors can be associated with an individual having diabetes. Although our cells do malfunction sometimes during gene expression, they make us the way we are today. You could not be you without gene expression and the central dogma. 

Next week: Model Organisms

References:

   (1)   This video shows the provides a basic understanding of the process cess that is done in the Central Dogma. Central Dogma of molecular biology. Khan Academy Medicine. https://www.khanacademy.org/test-prep/mcat/biomolecules/amino-acids-and-proteins1/v/central-dogma-of-molecular-biology-2. Accessed February 6, 2019. 

   (2)   This is the 4th edition Essential Cell Biology textbook. Alberts, B., Bray, D., Hopkin, K., Johnson, A., Lewis, J., Raff, M., Roberts, K., Walter, P. Essential Cell Biology. Fourth Edition. New York, United States. Published by Garland Science, Taylor and Francis Group, etc. Most recent copyrights were in 2014. (p. G:24, G:10, & 262).

   (3)   This manuscript describes gene expression and how certain diseases and syndromes happen because of how genes are expressed. Transcriptional Regulation and its Misregulation in Disease. NCBI. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640494/. Published March 14, 2013. Accessed February 8, 2019. 

(4)   This site has a video and facts about our DNA, the human genome, and how our DNA makes us unique. What are DNA and Genes? Learn. Genetics. https://learn.genetics.utah.edu/content/basics/dna. Accessed February 9, 2019. 

(5)  This site describes the process of how the body regulates blood sugar levels. Healthwise staff. How the Body Controls Blood Sugar. HealthLink BC. https://www.healthlinkbc.ca/health-topics/uf6060. Updated May 3, 2017. Accessed February 13, 2019.