BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: Enzymes

The Compound with the Potential to Decimate COVID-19 Morbidity  

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.”

Several vaccines (2021)

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?

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?

Prozac pills

A Friendzyme of the Environment

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.

 

File:PETase active site.png - Wikimedia Commons

^ The enzyme PETase 

 

 

 

 

 

 

 

 

 

 

 

 

 

Nobel Prize awarded to Researchers for Key Discoveries in Cellular Respiration

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

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.

 

Powered by WordPress & Theme by Anders Norén

Skip to toolbar