The Mystery Molecule Page: 2009

December

 

A fragment of this molecule causes a common gastrointestinal disease, which will be the topic of our December Northern California section meeting. Can you guess what it is?

2009 December Molecule

Gliadin
Gluten is the protein component of the endosperm of grain kernels, and flour contains small soluble proteins called gliadins. These contain a segment which is relatively resistant to protease digestion and which, when expressed on the surface of antigen presenting cells, incites an intense inflammatory response. Overtime, the absorptive villi of the small intestine become blunted and malabsorption ensues. This disorder, called celiac disease, was once considered to be of low prevalence but is now known to affect almost 1% of individuals of European descent. It has become a significant condition to rule out when patients complain of chronic diarrhea. The entire presentation is posted on the Northern California section website.


November

 

This sulfamate-substituted monosaccharide (used in the past as an anticonvulsant) looks a little bit like a wishbone and it may help you deal with the Thanksgiving turkey. Can you guess what it is?

2009 November Molecule

Topiramate
This generic anticonvulsant makes people feel satiated. Combined with phentermine, a well-known appetite suppressant which was part of the infamous “fen-phen” diet drug, it is one of several new weight-loss drugs which have completed clinical trials and will be reviewed by the FDA soon. We hope that you had a great Thanksgiving


October

 

At this year’s Bay Chem meeting on October 9, you will hear about new alternatives to this classic marker of cardiovascular disease. Can you guess what it is?

     

Troponin
Bay Chem began with a presentation by Dr. Alan Wu describing novel markers of acute coronary syndrome but troponin continues to be the most commonly used marker at the current time. In this image, troponin T (the portion which attaches to tropomyosin) is purple; troponin I (the portion which interferes with the actin-myosin interaction) is blue and troponin C (the portion which interacts with intracellular calcium) is green.


 

  September

This antibiotic was recently discovered to be a potent killer of breast cancer stem cells and may represent a new class of chemotherapeutic agents. Can you guess what it is?

   

Salinomycin
This potassium ionophore, commonly used as an antibiotic in farm animals, was one of a few compounds out of over 16,000 screened by researchers at the Massachusetts Institute of Technology that showed effectiveness against breast cancer stem cells. These are often resistant to conventional chemotherapy and this discovery may provide a new way to target such regenerating cells.

 


 

August

This molecule is currently at the center of the investigation into the death of singer Michael Jackson. Can you guess what it is?

   

Propofol
This hypnotic drug is used by anesthesiologists because it induces anesthesia rapidly and its effect is also very short-lived. It is contraindicated when the patient is taking benzodiazepines. The Los Angeles County coroner recently determined that Michael Jackson’s death was caused by the combination of propofol and lorazepam, and it has been ruled a homicide.

 


July

This membrane protein will be the topic of one of the plenary lectures at this year’s AACC annual meeting. Can you guess what it is?

 

Aquaporin
Dr. Peter Courtland Agre's plenary lecture described this family of water channel proteins found throughout nature and responsible for numerous physiological processes in humans. Aquaporins have been implicated in multiple clinical disorders—including fluid retention, bedwetting, brain edema, cataracts, heat prostration, and obesity. For his work describing these proteins, Agre shared the 2003 Nobel Prize in Chemistry with Roderick MacKinnon of Rockefeller University.


 

 June

This molecule, previously used to monitor HIV infection and cancer, is the latest proposed marker of cardiovascular risk. Can you guess what it is?

 

 

 

 

Neopterin
A member of the class of compounds (called pteridines) that also includes a component of folate, neopterin is synthesized by macrophages after they are stimulated by interferon-gamma by T cells. It appears to enhance inflammation by a variety of mechanisms. It has been primarily used as a prognostic marker in HIV infection but the report in last month’s issue of Clinical Chemistry by Grammer et al described its potential usefulness as an independent predictor of cardiovascular risk.


 
 

 

May

This molecule, so important to motherhood, will no doubt be a focus of Dr. Judy Stone’s presentation at our May meeting soon after Mother’s Day. Can you guess what it is?

 

 

 

Estradiol
Dr. Stone reviewed the trials and tribulations of using liquid chromatography/tandem mass spectrometry (LC/MSMS) for a variety of analytes, including steroid hormones. Much of the focus of LC/MSMS has been on testosterone but estradiol measurement may also benefit from this approach, especially when enhanced analytical sensitivity is needed.


April

 

 

 

 

This molecule will be the focus of Dr. Thomas Bersot’s discussion at our April meeting in Berkeley. Can you guess what it is? 

April 2009

 

 

C-reactive protein
Dr. Bersot reviewed the results of the recent JUPITER trial which showed that measuring levels of this non-specific inflammatory marker using high-sensitivity assays may be helpful in deciding whether or not to start statin therapy in patients without significantly elevated LDL cholesterol levels. He mentioned that CRP is a “pentraxin” protein, which in Greek means “five berry bushes” – a feature nicely shown in this image.



March

This molecule has been in the news because of problems assaying it at a commercial laboratory as well as Medicare considering not paying for its measurement, and it was the focus of last month’s Northern California AACC meeting. Can you guess what it is?

 

 

Vitamin D
Pictured is 1,25-dihydroxy-vitamin D, to be specific. At our February meeting, Dr. Darryl Erik Palmer-Toy from Kaiser Permanente Reference Laboratories reviewed methods used to detect vitamin D and Dr. Sridevi Devaraj from UC Davis Medical Center covered clinical applications in diabetes. The indications for ordering this test remain controversial, but there is no question that vitamin D has become a major analyte in recent years.

 


 

February

Cole Porter called love “a chemical reaction, that’s all” and scientists reported in Nature last month that this molecule may be elevated in all of us on Valentine’s Day. Can you guess what it is?

 

 

 

Oxytocin
Neuroscientist Larry Young at Emory University has discovered that female prairie voles become very attached to the nearest male when their brains are infused with oxytocin, a hormone produced by the posterior pituitary involved with lactation. Similarly, male voles become interested in the nearest female when their brains are infused with a similar posterior pituitary hormone (vasopressin, also known as anti-diuretic hormone). Whether these hormones are involved in human “love” remains to be seen!


 

January

Daniel Gajdusek, who died last month, was co-winner of the Nobel prize in medicine for describing a disease caused by a protein which undergoes isomerization (and the abnormal folding) shown in the figure. Can you guess what it is? 

 

 

Prion
Gajdusek helped to show that “kuru”, a degenerative neurological disorder in New Guinea, was transmissible by injecting diseased brain tissue into chimpanzees. The disorder (caused by the New Guinea natives eating of deceased tribesmen’s brains) is now known to be a transmissible spongiform encephalopathy (TSE) caused by a protein which undergoes a change in its secondary structure (from helical to pleated sheet) resulting in abnormal function. The abnormal protein (called a prion) is able to induce similar folding abnormalities in normal proteins (making it an “infectious” agent, even though it is not “alive”).

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