Enzymes – BioQuakes

Tag: Enzymes

The Cleanup Crew: PLD3 and PLD4

On January 20, 2025

Scientists at Scripps Research have made significant strides in their understanding of PLD3 and PLD4, two essential enzymes that break down nucleic acids such as DNA and RNA in cells. These enzymes aid in the prevention of nucleic acid accumulation. Nucleic acid accumulation can activate the immune system and result in autoimmune and immune disorders including lupus, Alzheimer’s disease and rheumatoid arthritis if left unchecked. Rheumatoid arthritis is a chronic inflammatory disease that can damage more than just one’s joints. This disease can affect a variety of body systems, including the skin, eyes, lungs, heart and blood vessels. PLD3 and PLD4 aid in the prevention of the diseases above by cleaning up the cellular environment and setting the threshold for what is considered an infection or not. Wow – I didn’t know these enzymes were so important to your health! Did you know about these enzymes?

The scientists were able to observe how the enzymes interact with their substrates during the degradation process by using X-ray crystallography to generate extremely precise, nearly atomic level models of these enzymes in different stages. X-ray crystallography first generates a photo that shows the pattern of diffracted x-rays, which scientists then use to develop a map of the enzyme’s molecular structure. Observing these models in various stages, the researchers found that both PLD3 and PLD4 use a two-step process to break down the nucleic acid. The enzyme first cleaves and links the DNA strand and separates a single nucleotide from the rest of the strand. Then, the enzyme releases this nucleotide.

Due to the fact that the enzymatic reaction described above occurs so quickly, the scientists used an alternative substrate to observe the enzyme’s structure during catalysis. The scientists incubated the enzymes together with a molecule that acted similarly to the substrate that the enzyme normally degrades (nucleic acid). However, the enzyme degrades this molecule much more slowly. After analyzing this slowed-down version of the enzymatic reaction between PLD3/PLD4 and nucleic acid, the scientists surprisingly discovered the function of phosphatase activity in both of the enzymes. How interesting!

The study also examined PLD3 and PLD4 mutations associated with diseases, specifically those connected to spinocerebellar ataxia and Alzheimer’s disease. While certain mutations led to reduced enzyme activity, making it more difficult to eliminate nucleic acids, others, including those associated with late-onset Alzheimer’s, enhanced enzyme activity. What a surprise! However, this increased enzyme activity seemed to lead to the instability and aggregation of the enzyme which are frequently linked to neurodegenerative diseases. After reaching these findings, the researchers are beginning to think about potential treatment plans. Some possible treatments include inhibiting the enzymes in cases where they are overactive. Other treatment ideas include replacing the enzymes in individuals who have non-functional versions of the enzymes. Can you think of any other possible treatment ideas that could work?

This article connects to AP Biology because it demonstrates the significance of enzymes. Enzymes are significant because they are vital to nearly every biological process due to the fact that they speed up chemical reactions that are necessary for life. More specifically, they are proteins that catalyze reactions, helping to break down molecules, build new ones, and maintain cellular processes.

However, as discussed in AP Biology, enzymes are susceptible to environmental influences such as temperature, pH, and substrate concentration. If these environmental factors are not within a specific range, the enzymes may not function to their fullest potential. For example, as temperature increases, enzyme function will increase until the enzyme ultimately denatures at a temperature that is too hot. When the temperature becomes too hot, the shape of the enzyme will change because the quaternary, tertiary, and secondary protein structures of the enzymes will be destroyed, leaving simply the primary structure (covalent bonds). Similarly with pH, specific enzymes have their own optimal pHs in which they can function best. If the pH deviates from this optimal pH, the increase of OH-/H+ will disrupt the quaternary, tertiary, and secondary protein levels of the enzyme and cause the protein to denature. In both of these cases, the quaternary, tertiary, and secondary protein levels were destroyed because their bonds such as hydrogen bonds, van der Waals interactions, disulfide bonds, ionic bonds, hydrophobic interactions are not strong enough to withstand extreme conditions. Lastly, substrate concentration can also affect the function of the enzymes. As the amount of substrate increases, the enzyme function increases until the enzyme function plateaus because the enzyme can only bind to so many substrates.

In the context of the study, when PLD3 and PLD4 activity is disrupted either by environmental factors or genetic mutations that alter their structure, nucleic acid accumulates which may lead to conditions like autoimmune diseases or neurodegenerative disorders. The study highlighted how mutations in these enzymes could reduce their activity or make them overactive, both of which could have harmful effects. Overall, the findings in the study emphasize the significance of understanding how enzyme function is influenced by environmental factors and other influences, as imbalances can contribute to dangerous responses such as disease.

Personally, this article made me even more grateful for my health. I realized that even little changes in my body could potentially cause major health issues. I am also grateful for the individuals who are researching about human health and improving society each day!

Penicillin Strikes Back

By prestandna

On January 20, 2025

In Student Post

Penicillin has been a cornerstone in the fight against bacterial infections for over 80 years, but as bacteria evolve, many have become resistant to this once-unstoppable antibiotic. However, a recent breakthrough in research could help restore penicillin’s power against these resistant strains. This new discovery involves combining penicillin with an enzyme inhibitor to prevent the breakdown of the antibiotic by bacterial enzymes, offering a promising new strategy in the battle against antibiotic resistance.

The research focuses on a specific group of bacteria that produce an enzyme called beta-lactamase. This enzyme breaks down penicillin and other beta-lactam antibiotics, rendering them ineffective. However, scientists have discovered that when penicillin is combined with an inhibitor that blocks beta-lactamase, it can remain effective against these resistant bacteria. This finding is exciting because it doesn’t require creating entirely new antibiotics; instead, it enhances the effectiveness of an existing antibiotic by pairing it with a simple compound.

Beta-lactamase resistance has been one of the biggest challenges in treating infections with penicillin, but by inhibiting this enzyme, penicillin can work properly again. The compound used to inhibit beta-lactamase prevents the enzyme from breaking down penicillin, allowing the antibiotic to continue targeting bacterial infections. This discovery could dramatically improve treatment outcomes for patients battling antibiotic-resistant infections.

This approach is groundbreaking because it doesn’t involve developing new antibiotics from scratch, which can take years and cost millions of dollars. Instead, scientists are exploring how existing antibiotics can be paired with other compounds to boost their effectiveness. This could significantly extend the life of penicillin and other antibiotics, helping us stay ahead of evolving bacterial strains.

In AP Biology, we learned that penicillin functions as a co-factor for certain enzymes. A co-factor is a non-protein molecule that helps enzymes carry out their reactions more efficiently. This new discovery ties into that concept because it shows how penicillin not only inhibits bacterial cell wall synthesis but also interacts with enzymes like beta-lactamase to regulate their activity. Understanding penicillin’s role as a co-factor helps explain why it can be so effective at targeting bacteria, and why pairing it with enzyme inhibitors could restore its power against resistant strains.

The idea of co-factors—whether organic molecules like penicillin or metal ions—was something that I found particularly interesting in class. Penicillin’s role as a co-factor isn’t just about its antibacterial action; it also highlights how it interacts with bacterial enzymes to influence their behavior. Seeing how these biochemical principles are applied in real-world solutions is exciting, especially when it comes to addressing major health challenges like antibiotic resistance.

This topic is especially interesting to me because I’m allergic to penicillin. Learning about how it works as a co-factor in enzyme reactions and how recent research is finding new ways to combat resistance has made me realize how much more there is to learn about this antibiotic, even after so many years of use. It’s fascinating to think that penicillin still has the potential to evolve in response to antibiotic resistance, and this new research proves just how important it is to keep exploring its properties.

As antibiotic resistance becomes an increasingly global issue, this research offers hope for the future—not only in overcoming resistance but in finding smarter ways to use the antibiotics we already have.

What do you think about the recent discoveries regarding penicillin’s effectiveness against resistant bacteria? Do you think this research will help manage the growing issue of antibiotic resistance? I’d love to hear your thoughts in the comments!

Uncovering the Deep Enzyme Pockets Behind Parkinson’s and Cancer

By metamorgosis

On January 9, 2025

In Student Post

There are approximately 75,000 different enzymes in the human body. These abundant proteins serve such a variety of roles in our bodies’ systems, we would truly not function the same without them. Nevertheless, enzymes can also become involved in the development of diseases such as Parkinson’s and even some cancer types.

One specific family of enzymes named the GTPases are often involved in these diseases. Science Direct classify GTPases as enzymes that facilitate the “conversion of guanosine triphosphate (GTP) to guanosine diphosphate (GDP).” Specifically, the reason this enzyme family has been historically deemed “undruggable” is related to the slippery exterior of the enzyme that made it difficult for modern drugs to target the disease-causing enzymes.

In September of 2024, researchers at the University of California San Francisco (UCSF) discovered a method for targeting the infamous K-Ras protein, a member of the GTPase family responsible for “up to 30% of all cancer cases.”

Structure of K-Ras Protein.

This enzyme and others like it work to regulate molecular movement and cell functions, so when an issue arises in these networks, diseases can easily develop. At UCSF, the team manipulated a K-Ras mutation to find new drug-binding sites that were previously unable to be seen by other drug discovery tools. Essentially, the mutation nudged open a pocket in the GTPases where the drug could bind, “freeze” the enzyme, and successfully inhibit a GTPase.

As we have learned in AP Biology, enzymes are globular proteins that are organic catalysts in living things. Enzymes work by lowering the amount of activation energy needed for a reaction to occur, and they do this by weakening the bonds between molecules and bringing them closer together to react with one another. Moreover, enzymes catalyze reactions by binding to one or more reactant molecules called substrates in the enzyme’s active site. This enzyme-substrate complex binds in a way that either a chemical bond-breaking or bond-forming process takes place, ending with the products of the reaction leaving the active site.

Meanwhile, enzyme inhibitors — such as the drugs studied by the UCSF researchers — can bind to the active site or another area of the enzyme and prevent the substrate(s) from binding and inhibit the reaction from happening.

According to the National Cancer Institute, an enzyme inhibitor is “a substance that blocks the action of an enzyme.” Relating to the significance of the researchers’ findings, this source explains that “In cancer treatment, enzyme inhibitors may be used to block certain enzymes that cancer cells need to grow.”

Illustrative comparison between enzyme catalysis and enzyme inhibition.

Groundbreaking research like this is becoming increasingly important for our understanding of the widespread diseases we face. Learning about the current innovative work of researchers is incredibly fascinating, as their work has significant implications for future enzyme research. It is truly exciting to see what researchers will investigate next in the field chemical genetics. What do you think will be the next step in enzyme research?

Fighting the Flu: Why Kids Need More Influenza Antivirals

By slayerson

On January 8, 2024

In Student Post

Influenza, otherwise known as the flu, is a very well known disease, that is unfortunately still very common. Given its commonality, there are many different ways to try and treat or mitigate the virus. Despite this fact, we can see discrepancies between guidelines and actual prescription practices for flu treatment among children, thanks to the study “Trends in Outpatient Influenza Antiviral Use Among Children and Adolescents in the United States.”

The lead author, James Antoon, a professor and doctor at Vanderbilt, emphasizes that antiviral treatment, especially when administered early, significantly improves health outcomes in influenza cases among children. However, the study reveals that a significant proportion of children, particularly those under the age of 5 and especially those under 2, are not receiving the recommended antiviral treatments. In fact, only about 40% of children studied were treated with antivirals, despite guidelines suggesting that all of them should receive this treatment.

Interestingly, the study reveals a notable disparity in the geographic use of influenza antivirals, showing a significant difference in prescription rates across different regions, independent of flu cases.

The reasons behind the under prescription of antivirals in children is likely due to various factors, including differing perceptions about effectiveness, variations in the interpretation of diagnostic testing, misunderstanding of national guidelines, and concerns about potential adverse drug events associated with certain antivirals, such as oseltamivir.

Additionally, the study mentions a previous investigation led by Antoon that explored neuropsychiatric side effects in children diagnosed with influenza. While these events are relatively infrequent, the study observed that they occurred in both treated and untreated children.

The research emphasizes the importance of improving flu management among vulnerable children in the United States, highlighting the need for better following of guidelines regarding antiviral use in pediatric flu cases.

This study connects to a few things we’ve learned this year in our AP Biology class. The way oseltamivir works, is that once inside, your body metabolizes it, which activates the oseltamivir. Once activated, it binds to and inhibits the active sites of the enzymes responsible for spreading the flu throughout a host’s body. As we learned in AP Biology, it doesn’t completely stop the spread of the virus, but it definitely slows it down, allowing your white blood cells to eradicate the virus.

Do you think the underuse of antiviral medications in children with influenza is a widespread issue? How might this research impact pediatric healthcare practices in managing flu cases more effectively?

(Post Includes suggestions made by ChatGPT)

Breakthrough at MIT: Cutting and Replacing DNA Through Eukaryotes

By cornophyll

On October 23, 2023

In Student Post

Scientists working at the Massachusetts Institute of Technology’s (MIT) McGovern Institute for Brain Research have found thousands of groundbreaking enzymes called Fanzors. Fanzors – produced in snails, amoeba, and algae – are RNA-guided enzymes. These enzymes combine enzymatic activity with programmable nucleic acid recognition, allowing a single protein or protein complex to aim at several sites. These enzymes were previously found in prokaryotes, like bacteria.

An example of one of these enzymes is CRISPR, which instead of coming from Eukaryotes like the new Fanzors, “CRISPR technology was adapted from the natural defense mechanisms of bacteria and archaea, a domain of relatively simple single-celled microorganisms”, according to LiveScience. Similar to Fanzors, these enzymes could alter genetic information and how the cell functions.

Orange ssDNA target bound to a type-I CRISPR RNA-guided surveillance complex (Cas, blue).

Although similar enzymes to Fanzors have existed, McGovern Fellow Jonathan Gootenberg says, “Eukaryotic systems are really just a whole new kind of playground to work in.” Eukaryotic cells carry membrane bound organelles, such as a nucleus, which holds genetic information, and a mitochondrion, which produces energy, but neither are found in prokaryotic cells, which have no membrane bound organelles. Eukaryotes are also the basis for both unicellular and multicellular organisms, while prokaryotic cells have no membrane bound organelles, and are solely the basis of unicellular organisms. Eukaryotes are found in animal cells, just like ours, while prokaryotic cells are found in bacteria and archaea. Furthermore, TechnologyNetwork says that prokaryotic cells are much smaller than eukaryotic cells “measuring around 0.1-5 μm in diameter”, while, “eukaryotic cells are large (around 10-100 μm) and complex”.

Eukaryotic cell and its organelles (left) and a prokaryotic cell and its flagella, or tails (right) [NDLA]

As Gootenberg said, all these differences prove that a brand new pathway to further developments has been unlocked. Research has shown that these eukaryotic cells carrying the enzyme have developed the gene cutting enzyme over many years, separate from the development of bacterial enzymes. It is believed that this makes them far more efficient and precise than past enzymes. Fanzors are found to cut targeted DNA sequences with 10-20% efficiency, while other programmable RNA guided enzymes found trouble targeting a single sequence and often attacked others. Ultimately, this discovery is a major breakthrough and will lead to further developments in the process of cutting and replacing DNA.

How do you expect or want this new discovery to be utilized? Are you excited for the new avenues for research Fanzors can create? Let me know in the comments!

How Baby Kangaroos Are Helping Climate Change

By ellectron

On March 5, 2023

In Student Post

In the world, there are over 1 billion cows and calves, roughly 4.3 times as many cows as people living in the United States. Cows are the number one source of greenhouse gases worldwide, with a single cow producing 220 pounds of methane gas a year. Methane (CH4) is a colorless, odorless, and highly flammable gas, composed of carbon and hydrogen. Being a potent greenhouse gas, it impacts climate change by increasing global warming according to the US Environmental Protection Agency. Methane affects our environment but it can also impact humans “high levels of methane can reduce the amount of oxygen breathed from the air. This can result in mood changes, slurred speech, vision problems, memory loss, nausea, vomiting, facial flushing, and headache. In severe cases, there may be changes in breathing and heart rate, balance problems, numbness, and unconsciousness“. Although this is in extreme cases. Recently, scientists may have discovered a methane inhibitor that could reduce the amount of methane cows release. This source comes from an interesting source though: Baby kangaroo feces.

Researchers from Washington State University wanted to figure out a solution to lower methane gas production rates in cows seeing as people enjoy eating red meat and taking them entirely out of the equation is not a feasible answer. They performed a study using baby kangaroo fecal matter to develop a microbial culture that inhibited methane production in a cow’s stomach stimulator. This resulted in cows producing acetic acid – is also known as ethanoic acid, ethylic acid, vinegar acid, and methane carboxylic acid; it has the chemical formula of CH₃COOH. Acetic acid is a byproduct of fermentation and gives vinegar its characteristic odor. Vinegar is about 4-6% acetic acid in water – in place of methane. Acetic acid is not just a waste product in a cow like methane but is actually beneficial for the cow as it helps muscle growth. Not only would lowering rates of methane production in cows be beneficial for the environment but also for the cow as the cow wastes around 10% of its energy in methane production. Researchers have tried chemical inhibitors but the methane-producing bacteria has become resistant each time. The actual experiment all began with the researcher’s study of fermentation and anaerobic processes, which lead to the creation of an artificial lumen designed to stimulate cow digestion. Then they began investigating how they could outcompete the methane-producing bacteria and learned that – specifically – baby kangaroos have acetic acid-producing bacteria instead of methane-producing bacteria. Researchers were “unable to separate out specific bacteria that might be producing the acetic acid, the researchers used a stable mixed culture developed from the feces of the baby kangaroo.” Eventually, the acetic acid bacteria was able to replace the methane-producing microbes for several months having similar growth rates. Researchers hope to eventually test their system outside of a stimulated rumen and on a real cow sometime in the future. This connects to our unit of enzymes and enzyme inhibitors. Enzymes allow the cell to perform tasks with less energy by binding to reactant molecules and holding them in a way that breaks the chemical bond allowing bond-forming processes to take place more easily. Enzyme inhibitors are molecules that bind to the active site – competitive inhibition – or the allosteric site – noncompetitive inhibition – making the enzyme unbindable, reducing the rate of enzyme-catalyzed reaction, or preventing it from happening altogether. This is what the researchers are trying to do in their study, inhibit the enzyme in the methane-producing bacteria and allow the acetic acid bacteria to grow instead. Overall, if this process proves to work in real cows it could be a huge advancement in the slowing down of climate change.

Revolutionizing Photosynthesis: The Power of Rubisco Enzyme Engineering

By Joshmosis

On March 5, 2023

In Student Post

Enzyme engineering has the power to create several new discoveries and possibilities in the evolutionary field. Questions that were not answerable through decades of really hard biochemistry have now become accessible by integrating this evolutionary perspective. In the past, Rubisco faced many issues, such as starting to catalyze an undesired reaction, in which it mistakes O2 for CO2 and produces metabolites that are toxic to the cell. In the article by the Max Plank Society, researchers have discovered that the Rubiscos that show increased CO2 specificity recruited a novel protein component of unknown function, through resurrecting and studying billion-year-old enzymes in the lab using a combination of computational and synthetic techniques.

According to this article by Alejandra Manjarrez that analyzes that research, form I rubisco has the highest specificity for carbon dioxide and the most efficient catalytic activity. Form I Rubisco is made up of eight identical catalytic large subunits and eight identical small subunits. Researchers suspected that its enhanced ability to discriminate CO2 from chemically similar molecular oxygen could be related to the presence of these small subunits since no other forms of Rubisco have them.

For years, research focused on changing amino acids in Rubisco itself, but new findings suggest that adding new protein components to the enzyme could be more productive. Rubisco is the most prevalent enzyme on the planet and is the key enzyme responsible for photosynthetic and chemoautotrophic carbon fixation and oxygen metabolism. It catalyzes the fixation of atmospheric CO2 to ribulose-1,5-bisphosphate (RuBP) to form two molecules of 3-phosphoglycerate (3PGA). This is the first part of the Calvin cycle which, as you learned in class, involves using atmospheric carbon dioxide, ATP, and NADPH to create G3P, which is the building block of glucose, through the processes of carbon fixation, reduction, and regeneration of the CO2 acceptor. With the new improvements in the efficiency of Rubisco and enzyme engineering as a whole, plants may be able to combat the increasing amount of carbon dioxide emissions hurting the earth through improved photosynthesis.

Can Enzymes Be the Solution to the Single-use Plastic Pollution Crisis?

By almoschetto

On December 21, 2022

In Student Post

Single-use plastic pollution, a massive issue that has been harming our planet’s environmental health for decades, might be able to be tackled with something as small as an enzyme.

Researchers Jen Dubois of Montana State University and John McGeehan of the University of Portsmouth have discovered enzymes that break down elements of single use plastic. These remarkable microbiological tools, called PETase and MHETase, have the ability to breakdown terephthalate polyethylene—one of the building blocks of (PET) plastic.

So, how does it work? How do these enzymes essentially eat plastic? PET is a polymer, which is a mega-protein made up of many smaller molecules (monomers). With the help of PETase and MHETase, these enzymes break the plastic down into “chemical building blocks”: ethylene glycol (EG) and TPA. Evidently now, a problem arises that concerns where these byproducts of the enzyme’s activity can go next. Thankfully, EG is a product that is useful for many everyday items, such as being an ingredient in antifreeze solution used in cars. But researchers can’t tell the same story for TPA; There is essentially no use for a chemical like this outside of PET plastic. So, with inspiration from the mechanism that made this byproduct in the first place, the Portsmouth research team thought the creation or discovery of another enzyme could do the job of breaking down TPA in the same way as for PET plastic.

Researchers from Michigan State University did just that, and found a solution to the overwhelming amount of TPA byproduct from PETase/MHETase activity of breaking down PET plastic. TPADO, an enzyme that breaks down TPA byproducts, was introduced, and was soon found to have incredibly binding ability to TPA—so much so that its fit into the chemical is described as “a hand in a glove.” In other words, the active site, the groove on the surface of the TPADO enzyme, fits perfectly with its substrate, TPA, by matching its exact shape, charge, and type of relationship with water (either hydrophobic or hydrophilic).

This groundbreaking research due to the collaboration of many researchers across several universities has revealed the long awaited light at the end of a very dark tunnel environmentalists call ‘the plastic crisis.’ With around 400 million tons of plastic discarded and then scoured all over the earth every year, the human race produces a weight of single-use plastic trash that is almost equivalent to the mass of the whole human population. But, with enzymes like PETase, MHETase, and now TPADO, modern science is now able to convert plastic waste into valuable molecular ingredients for other products, essentially minimizing waste in not only the plastic industry, but others, as well.

Still, these researchers’ jobs are not done, and they know it. TPADO has been tested under powerful x-rays to show its exact shape and molecular structure and reveal its innerworkings. With information like this, the world of enzyme engineering can be improved to make artificial ones that are more efficient and more useful.

So, something as small as enzymes can be the solution to the single-use plastic crisis we have here on planet earth? The answer is ‘yes’, thanks to modern science and dedicated researchers at the universities of Montana, Portsmouth, and Michigan State.

Image of single-use plastic waste.

The Redesigning of CRISPR

By rokhsarscov2

On March 20, 2022

In Student Post

Cas9, a key component of a widely used CRISPR-based gene-editing tool has been redesigned by scientists at The University of Texas at Austin to be thousands of times less likely to target the wrong stretch of DNA while remaining just as efficient as the original version. This could potentially make gene replication safer and more abundant for medical use.

The CRISPR-Cas9 system consists of an enzyme that introduces a change or mutation into DNA. Cas9 enzymes can cut strands of DNA at a specific location in the genome so parts of the DNA can then be added or removed. CRISPR-based gene-editing tools are adapted from naturally occurring systems in bacteria. In nature, Cas9 proteins search for DNA with a very specific sequence of 20 letters. When most of the letters are correct, Cas9 could still change these DNA fragments. This is called a mismatch, and it can have disastrous consequences in gene editing.

The challenge with using CRISPR-based gene editing on humans is that the molecular machinery occasionally makes changes to the wrong section of a host’s genome. This could possibly repair a genetic mutation in one spot in the genome but may accidentally create a dangerous new mutation in another.

SuperFi-Cas9 is the name of the new version of Cas9 which has been studied and proven to be 4,000 times less likely to unnecessarily cut off-DNA sites but operates just as fast as naturally occurring Cas9. In the Sauer Structural Biology Lab, scientists were surprised to discover that when Cas9 encounters a type of mismatch, there is a “finger-like structure” that swoops in and holds on to the DNA, making it act like the correct sequence. Usually, a mismatch leaves the DNA unorganized since this “finger-like structure” is mainly used to stabilize the DNA. Based on this insight, scientists redesigned the extra “finger” on Cas9 so that instead of stabilizing the part of the DNA containing the mismatch, the finger is stored away which prevents Cas9 from continuing the process of cutting and editing the DNA. This result in SuperFi-Cas9, a protein that cuts the right target just as readily as naturally occurring Cas9, but is much less likely to cut the wrong target.

This applies to our unit on mitosis when cells are replicating DNA in the S-phase. When chromosomes are duplicated, gene replication occurs. Sometimes gene replication could result in mutations which could lead to a cell not functioning properly. A cancerous cell is an example of cell not performing normally since it rapidly performs mitosis causing the cell to duplicate uncontrollably. This results from an abnormality in gene replication where CRISPR technology can locate this mutation and restore the cell back to normalcy.

The Compound with the Potential to Decimate COVID-19 Morbidity

By elendometrium

On January 17, 2022

In Student Post

Severe cases of COVID-19 result in respiratory problems and blood clots. Scientists are currently looking for a molecular solution to enhance therapeutic treatment. According to the authors, immunometabolic suppression seems to be the the main contributor to the shut down of the immune system, leading to a more severe response from SARS-CoV-2. In severe cases of COVID-19, it seems that a certain family of phospholipases has been associated with determining the outcome of symptoms in patients. Higher levels of the molecule secreted phospholipase A2 and its 12 other variants have been prevalent in cases of cancer, sepsis, bacterial infections and atherosclerosis. Similarly, high levels of sPLA2 were found in 127 blood plasma samples from severely affected COVID-19 patients.

These new findings provide a potential path towards effective treatment for Coronavirus. In new research led by the University of Arizona, the overabundance of the active enzyme, secreted phospholipase A2 group IIA, in the human immune system has been associated with increased severity of COVID-19 symptoms faced by infected individuals.

Maintaining host resistance and disease tolerance is an important part of successfully fighting Coronavirus related infections. Secreted phospholipase A2 group IIA (sPLA2-IIA) is naturally circulated by the human body in order to defend against bacterial invaders. The average healthy individual typically circulates around half a nanogram per milliliter of sPLA2-IIA. Researchers found that 63% of COVID-19 infected individuals being monitored at Stony Brook Medical Hospital who circulated amounts greater than or equal to 10 nanograms per milliliter of sPLA2-IIA died from the symptoms of COVID-19.

Why would certain infected individuals circulate 20 times the healthy amount of sPLA2-IIA?

When the human body encounters bacterial pathogens, the secretion of the enzyme sPLA2-IIA protects the body against the pathogens in an innate defense. Therefore, in an attempt to combat Coronavirus, the human body secretes a greater amount of sPLA2-IIA. This increased amount of sPLA2 can be considered a double-edged sword. On the one hand, the enzyme aids in attacking the virus. On the other hand, the enzyme acts as a “shredder,” tearing apart the membranes of vital human organs. The attack on the host’s cell membranes leads to organ failure and death. Interestingly, the active enzyme sPLA2-IIA resembles an isotopic enzyme found in snake venom, which similarly destroys microbial cell membranes. Much like the active enzyme found in rattlesnake venom, sPLA2-IIA has “the capacity to bind to receptors at neuromuscular junctions and potentially disable the function of…muscles.”

By looking at the lipid metabolite levels in blood samples of Coronavirus patients, researchers were able to corroborate severe Coronavirus symptoms with an overproduction of sPLA2. It seemed that individuals whose circulatory systems contained elevated levels of lysophospholipids (lyso-PLs), unesterified unsaturated fatty acids (UFAs), acylcarnitines, and mitochondrial DNA as well as a decrease in plasma levels of phospholipids experienced higher mortality rates. Expectedly, there was cell energy dysfunction and unexpectedly high levels of sPLA2-IIA enzyme.

In the future, it is highly plausible that an sPLA2-IIA inhibitor may become a standard component of treatments distributed amongst patients with severe symptoms. Hopefully, such a treatment could help to diminish the ever rising mortality rate of Coronavirus and furthermore alleviate the suffering of thousands of patients.

Ultimately, our vast knowledge of molecular biology has an application beyond the mere observations of a published study. It is discoveries like this one that have the capacity to positively affect the course of a person’s life. My mother, for example, contracted COVID-19 a few weeks ago and had to endure days of intense fevers and coughing fits while she was confined to her bed. Although he never tested positive, my father too was bed-ridden with the same symptoms. In the meantime, I, a high school student, found myself taking care them as well as their household duties: cleaning the house, cooking three meals a day, doing laundry, etc. As a high school senior who has completed the college application process, I fortunately had the time to manage the extra workload. However, it is important to realize that many citizens around the world do not have the same privilege; some people are displaced from work while others catch the virus and never make a full recovery. With the robust power of anatomical science, we have the capacity to change people’s lives for the better.

PAXLOVID: A Breath of Fresh Air?

By hirshtology

On January 17, 2022

In Student Post

Right now, it seems like the only defense against the evasiveness of COVID is the vaccine. However, there has been a new emergence that might help alleviate some worries. This is the PAXLOVID anti-viral drug. This new drug is given to people with high-risk cases of COVID a few days after they are infected. Though, before this pill is approved, it has to run through many trials, and it has to be confirmed by the FDA (Food and Drug Administration). The numbers that are coming out of the trials of the drug are nothing short of astonishing….

Pfizer made the announcement that within 3 days of infection, the PAXLOVID drug reduces the risk of hospitalization or death by 89%. The trials for the drug were over a substantial amount of time. The numbers that have been received as of now are that out of 607 people tested, only 6 were hospitalized and NONE died. These are very promising numbers for the drug, and it is a big step towards approval. To further boost PAXLOVID’s credibility, placebo, a “control” drug was tested alongside PAXLOVID. This control drug is a fake pill to make people believe it is doing good for them. This is called the placebo effect. In the end, the fantastic numbers produced by PAXLOVID against placebo proved that PAXLOVID is the way to go and that it is a successful drug that actually works. Now you may be wondering how does this “anti-viral drug” work to defend against COVID?

The answer is not so simple. The primary goal for PAXLOVID, and any other anti-viral drug is to prevent the virus from replicating. As we learned in our biology class, the way a virus replicates itself is by entering the dendritic cell or macrophage, then it can actually copy RNA virus and take command of the cell, basically hijacking it. However, the anti-viral drug is made up of two clear components that instead of interfering with RNA copying enzyme, it blocks something else. The drug has the ability to inhibit Protease enzymes. Protease enzymes are mainly responsible for activating long strains of protein by cutting them down.

Altogether, PAXLOVID is a versatile, and very useful drug that we will likely be seeing and hearing more about in the near future. If you contracted COVID, would you be willing to take PAXLOVID?

A Friendzyme of the Environment

By marinebiolojohn

On October 20, 2020

In Student Post

A team of researchers at the University of Portsmouth in England have engineered an enzyme that breaks down plastic six times faster than the previous most efficient plastic destroying enzyme. This enzyme specializes in breaking down PET, polyethylene terephthalate, the material most plastic bottles are made of. They created this by reengineering the previous enzyme, PETase, and combining it with another enzyme, MHETase, to create a ‘super enzyme’. They used a method normally utilized by companies in the biofuel industry, who combine enzymes to break down types of cellulase. Granted, it is still far too slow to be effective in breaking down the vast amounts of plastic waste we are faced with, but it is certainly a step in the right direction.

Enzymes are made of proteins which are made up of amino acids. Amino acids consist of a carboxyl group, an amino group, and a unique R group. Amino acids create chains in which carboxyl group match with amino groups, linking together using covalent peptide bonds, formed after dehydration synthesis. The chains of amino acids begin to fold and create proteins, which are the basis of almost all enzymes.

I think this issue is an important endeavor that should be funded by governments all around the world. We all share the Earth, and it is currently under threat by a number of issues, a prime example being pollution. Up to 8.8 million metric tons of plastic waste may enter the oceans every year. Some studies put the amount of seabirds that contain some form of plastic waste in their system at upwards of 90%. Plastic waste needs solutions before it makes the oceans uninhabitable for more creatures, and a mass produced enzyme may be a valid solution. The Great Pacific Garbage Patch is a large convergence of currents in the Pacific Ocean that has collected so much garbage, a large portion of which is made of plastic, that it is comparable to the size of Texas. Developing an effective enzyme that could quickly break down plastic could become a serious help to minimizing the environmental impact of the Garbage Patch.

While we cannot develop enzymes ourselves, several tips for mitigating our plastic waste are:

-Try to use aluminum cans instead of plastic bottles.

-Always recycle or reuse plastic bottles.

-Cut the holes of six pack rings before disposing so animals cannot be caught in them.

-Use metal and paper straws as a substitute for plastic straws.

^ The enzyme PETase

Nobel Prize awarded to Researchers for Key Discoveries in Cellular Respiration

By michaelchondria

On October 23, 2019

In Student Post

Recent findings about the change in oxygen levels in cells show new important factors about oxygen that translate to one’s well-being. William G. Kaelin Jr., Sir Peter J. Ratcliffe and Gregg L. Semenza discovered how cells can “sense and adapt to changing oxygen availability,” and are now being awarded the Nobel Prize in Physiology or Medicine. Oxygen is a crucial aspect to how a cell’s functionality. Mitochondria in cells use oxygen to aid in converting food into ATP (energy), a process known as cellular respiration.

A representation of the reaction of cell respiration.

Gregg Semenza wanted to further look into the rise of levels of the hormone erythroprotein (EPO), a response to low levels of oxygen, or hypoxia. He found that “oxygen sensing mechanisms were present in virtually all tissues, not only in the kidney cells where EPO is normally produced.” While Semenza analyzing cultured liver cells, Semenza found a protein complex that was unknown to science. He named unidentified DNA segment the “hypoxia-inducible factor (HIF).”

Over the course of 24 years, Semanza continued to explore aspects of HIF and found two different DNA-binding proteins, now named “HIF-1a and ARNT.” Researchers worked with Semanza in finding out which parts of the HIF assist in cellular respiration. While Semenza and Ratcliffe were researching regulation of EPO, Kaelin Jr. was researching von-Hippel-Lindau’s disease (VHL). Kaelin Jr.’s research showed that VHL gene “encodes a protein that prevents the onset of cancer,” and that cancer cells lacking a functional VHL gene have “abnormally high levels of hypoxia-related genes.” But when the VHL gene was reintroduced into cancer cells, “normal levels were restored.” Eventually, Kaelin Jr. and his team found that VHL needs HIF-1a for degradation at normal oxygen levels.

Kaelin Jr. and Ratcliffe both published articles that center around protein modification called prolyl hydroxylation which “allows VHL to recognize and bind to HIF-1α degradation with the help of oxygen-sensitive enzymes.” The papers also wrote that the gene activating function of HIF-1α “was regulated by oxygen-dependent hydroxylation.” The researchers now had a much clearer idea of the effects of how oxygen is sensed within cells.

These groundbreaking finds give the science world more information about how oxygen levels are regulated in cells in physiological processes. Sensing oxygen levels is important for muscles during physical exercise, as well as the generation of blood cells and strength of one’s immune system.

Enzyme Protects Against Dangers of Oxygen

By leahna

On February 11, 2013

In Student Post

Yes, you read the title correctly: Oxygen can be dangerous.

As you may (or may not) remember, Oxygen is needed for two parts of cellular respiration. 1) For the Pyruvate made in Glycolysis to enter the mitochondria for the Krebs Cycle 2) As the final electron acceptor in the electron transport chain during Chemiosmosis. If there isn’t enough oxygen around (say, you’re running and there’s not enough oxygen to go to your muscle cells), the pyruvate made in glycolysis will not enter the mitochondria, but will instead undergo fermentation, which basically turns the NADH back into NAD+ so cycle of cellular respiration can continue.

Oxygen becomes dangerous when unhealthy cells fail to undergo cellular respiration, despite plentiful oxygen and instead undergo fermentation. This leads to uncontrollable cell growth: cancer. Luckily, scientists just discovered the enzyme superoxide dimutase, or SOD1 for short, regulates cell energy and metabolism by transmitting signals from oxygen to glucose to repress respiration. This happens through cell signaling, when SOD1 protects the enzyme Kinase-1 gamma, of CK1Y, an important key from switching from respiration to fermentation. The results of this study were published in the Journal “Cell” on January 17th.

This diagram shows how enzymes, like SOD1, work. The substrate binds to the active site of the enzyme and the enzyme either breaks the substrate in two or puts two substrates together.

The interesting thing about this study is that SOD1 is not a new discovery. Scientists have known about SOD1 since 1969, but they thought it only protected against free radicals. Researcher Valeria C. Culotta calls SOD cells “superheroes” because of their many powers: protecting against free radicles and regulating cellular respiration.

According to Vernon Anderson, PhD, the result of this study might find out why cells turn to fermentation, casing cancer and some other diseases.

BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: Enzymes

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Nobel Prize awarded to Researchers for Key Discoveries in Cellular Respiration

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