2014 Mystery Molecule

December

The Japanese manufacturer Takata switched to this molecule as the basis of the propellant in their air bags, with explosive results. Can you guess what it is?

Ammonium nitrate
Did you recognize the ammonium ion (NH4+) below the nitrate ion (NO3-)? This compound is used as a fertilizer (good source of nitrogen) but it is also the main component of many explosive devices (both legal and illegal). The original propellant in automobile airbags was sodium azide, a commonly used bacteriostatic agent in the clinical laboratory which we all know can be dangerous if it is too concentrated. Because it is also volatile, Takata (a major airbag producer) switched to a different explosive compound (tetrazole) in the mid-1990s. The recent switch from tetrazole to ammonium nitrate as the propellant is believed to have been an effort to reduce cost. Unfortunately, it may malfunction, especially in areas of high humidity, and explode with such force that it shatters the metal in the airbag casing. The National Highway Traffic Safety Administration is urging automakers to expand their recalls of cars with these airbags to other areas as well.


November

Eating a high-protein breakfast may increase levels of this molecule in your brain and allow you to resist gorging at your Thanksgiving dinner. Can you guess what it is?

Dopamine
Researchers at the University of Missouri recently reported that eating a high-protein breakfast increased the levels of dopamine in the brain. It also markedly reduced cravings for food (especially foods high in fat) during the day. They note that fewer Americans eat a healthy breakfast today and that this trend may contribute to the current obesity epidemic. Dopamine is a crucial chemical produced in the limbic system that creates “reward”. We hope that your Thanksgiving was very rewarding!


October

Last month a San Francisco supervisor made news when he announced that he was using these molecules, which are combined in one commercially available pharmaceutical. Can you guess what they are?

 

Emtricitabine and Tenofovir
These two anti-retroviral drugs have been marketed as a combination preparation called Truvada ® by the pharmaceutical company Gilead. The product is controversial because it is being marketed as prevention of infection with human immunodeficiency virus, and some have questioned whether this may cause individuals to ignore recommendations for safer sex. Both of the drugs are nucleoside reverse transcriptase inhibitors. Emtricitabine (top) was discovered at Emory University (perhaps explaining its name?) and is similar to a more commonly used drug called lamivudine. Tenofovir (bottom) was developed in the Czech Republic initially as an anti-viral for use against Herpes viruses.


September

Monoclonal antibodies against this molecule were used last month in an effective (but controversial) way. Can you guess what it is?

 

Ebola viral glycoprotein

The Ebola virus is an RNA virus that causes fever and hemorrhage. It is associated with a very high rate of mortality. The recent outbreak in Africa has not been contained as easily as previous ones, raising concern. Monoclonal antibodies directed against the glycoprotein that studs the viral surface (and allows for fusion with the infected host’s cell membranes) were used to treat some infected patients. The glycoprotein is a trimer made up of three dimers. One dimer forms a “chalice” and the other forms a “cradle”. Controversial elements of the use of the monoclonal antibody product last month include the lack of extensive testing, the limited supplies and, because the monoclonal antibodies are produced using tobacco plants instead of bacteria, the potential delay in ramping up production.


August

Millions of kids will pack this molecule into their suitcase this month (shown in the crystal structure that they will pick up on the beach). Can you guess what it is?

 

Calcium carbonate 

This molecule appears in a variety of forms in minerals and its inorganic chemistry can be complicated. It is also the major component of the shells of most marine organisms. Oyster shells, a source of calcium carbonate for medicinal purposes, are also a major source of entertainment for kids at the beach, and many sandy fragments are taken home as souvenirs of a summer vacation. We hope that yours was a great one!


July

Bring along something to munch on if you go to the plenary lecture about this molecule at the annual AACC meeting this month. Can you guess what it is?

 

Leptin

Jeffrey Friedman is a researcher who studies this key regulator of appetite and hunger. He discovered the gene that encodes the hormone in a strain of mice with mutations that prevent them from feeling satiety. Along with Douglas Coleman, the researcher at the Jackson Laboratory who first identified the mouse strain, Friedman won the Lasker award in 2010. In his plenary session, he described the mechanisms by which leptin restrains appetite, and how it may one day be used to treat obesity, lipodystrophy, and other disorders of fat distribution.


June

Last month, Coke decided to follow Pepsi with regards to this molecule. Can you guess what it is?

 

Brominated fatty acid

Last year, Pepsi announced that it was removing brominated vegetable oil from Gatorade, a popular sports drink. The substance had already been banned from food and drinks by the European Union because of concern over the accumulation of bromine in the body. Last month Coca-Cola announced that it was also removing the substance from Powerade, its sports drink, as well as all of its other products. Brominated fatty acids, used to keep certain ingredients in drinks from separating, will be replaced by sucrose acetate isobutyrate. Although both companies deny it, their action was probably influenced by a website set up in 2012 by a high school student in Mississippi to bring attention to the ingredient.


May

Oklahoma tried to substitute this molecule for thiopental as the first of the three-drug lethal injection cocktail last month, with disturbing results. Can you guess what it is?

 

Midazolam

This short-acting benzodiazepine has recently replaced sodium thiopental as the initial sedating drug used in executions in the U.S. Once the subject is unconscious, a muscle relaxant and potassium chloride are administered in order to stop breathing and stop the heart. Although it has apparently been used successfully in at least two executions, it failed last month, allowing the subject to regain consciousness as the additional two drugs were being injected. It is still unclear what went wrong. The prisoner did eventually die of a heart attack.


April

This month the FDA approved an easy-to-use device to inject this molecule when first responders suspect heroin overdose. Can you guess what it is?

 

Naloxone

The so-called "second chance drug", naloxone is an opioid antagonist with no agonist effect. It has been used for decades as an emergency treatment for heroin or morphine overdose as it quickly reverses depression of the respiratory system. Attorney General Eric Holder recently urged first responders to carry this molecule with them in order to be better able to resuscitate victims of overdoses. The FDA fast-tracked approval of a hand-held automatic injector of naloxone to help reduce the marked increase in deaths recently observed in the U.S.


March

This molecule is not a four-leaf clover, but any T lymphocyte "looking over" it would jump for joy. Can you guess what it is?

 

Phytohemagglutinin (PHA)

This lectin is especially plentiful in kidney beans. Its ability to agglutinate red blood cells gives it its name and also its potential toxicity when someone eats uncooked kidney beans. It is famous for inducing mitosis in T lymphocytes, and proliferation in response to PHA is used in the evaluation of immunodeficiency disorders. However, its major usefulness in the clinical laboratory is as a lymphocyte mitogen allowing the use of peripheral white blood cells for karyotype analysis as well as other cytogenetic investigations.


February

Americans like the taste of Hershey's chocolate, which uses a secret process that may produce this molecule, and other manufacturers actually add it to their recipe to enhance their sales in the U.S. Can you guess what it is?

 

Butyric acid

Many believe that Hershey's secret process involves the partial lipolysis of milk and that the production of butyric acid creates a distinct taste that differs from other types of milk chocolate. Despite the fact that the recent chocolate revolution has enhanced people's appreciation of bitter dark chocolate, Hershey's remains a market leader. We hope that your Valentine's Day was a sweet one!


January

A recent report that antibodies against this molecule helped shrink malignant melanoma tumors led Science magazine to call cancer immunotherapy the 2013 "breakthrough of the year". Can you guess what it is?

 

Programmed Death 1 (PD-1)

There are many approaches to "cancer immunotherapy" but the editors of Science focused on progress in enhancing T cell activity against epitopes on the surface of tumor cells using antibodies that prevent them from stepping on the brake. Tumor antigens (such as the classic CEA) were once considered novel tumor-specific proteins, but it soon became clear that very few (if, indeed, any) were not normal proteins whose expression was simply up-regulated in certain tumors. Because they were normal proteins, the immune system was tolerant of them. But by blocking the mechanisms that maintain tolerance, the immune system can be coaxed into attacking them. One such mechanism is a protein called PD-1 which, like another called CTLA-4, tells T cells not to react to antigen engaged by the T cell receptor. Monoclonal antibodies against these T cell "brakes" may be major cancer treatments in the future.