The Mystery Molecule Page: 2003

DECEMBER

This molecule will be sprinkled on egg nog this month but was once worn in a small bag around the neck to protect against plague. Can you guess what it is?

Isoeugenol
The molecule responsible for the smell of nutmeg is supposed to have repelled the fleas that carried bubonic plague. It is very similar to other molecules with very different aromas (including cloves and ginger). Thanks again to "Napoleon's buttons" by Penny Le Couteur and Jay Burreson.

NOVEMBER

This molecule will be the focus of debate at the dining room table later this month. Can you guess what it is?

 

Myoglobin
Slow-acting muscle fibers of long endurance depend on oxidative metabolism and are rich in myoglobin. This protein (with a heme group that, like hemoglobin, binds oxygen). makes these muscles dark red. More rapidly acting (white) muscles make use chiefly of glycolytic mechanisms. Human muscle is a mosaic of the two types of fibers but, in birds, they are often grouped into separate regions. Hope you had a nice Thanksgiving.

OCTOBER

This substance (four steps away from simple glucose) would have made Columbus’s voyage to the New World a lot more pleasant than it was. Can you guess what it is?

Ascorbic acid (Vitamin C)
Trans-Atlantic crossings in the 15th and 16th centuries usually resulted in mortality rates of over 50%, due to scurvy. In a new book about important historical molecules (Napoleon’s Buttons), the authors describe a randomized study performed in 1747 that showed how adding an orange or lemon to the sailors’ diet cured the disease.

SEPTEMBER

This drug was recently approved as an alternative to methadone treatment for heroin addicts. Can you guess what it is?

Buprenorphine
Previously used only as an analgesic, this drug does not have the sedative effect of methadone. It is growing in use but may not need to be included in toxic screens. Another benefit is that unlike methadone, it will not give the addict more than a mild high at any dose, reducing the chance of overdose.

AUGUST

Oxidation of this molecule will provide soothing sights on warm August nights (and a related compound is used in a popular automated immunoassay system). Can you guess what it is?

Luciferin
The carboxyl group on the right is oxidized by the enzyme luciferase, forming oxyluciferin and releasing light (chemiluminescence). This is how the firefly creates those tiny flashes of light. A different molecule (luminol) is oxidized by horseradish peroxidase (releasing light) in the Ortho-Clinical Diagnostics Vitros ECi instrument.

 

JULY

This molecule will dominate the 2003 annual meeting of the AACC in Philadelphia this month, especially the opening plenary session on Sunday. Can you guess what it is?

DNA
This should have been an easy one. J. Craig Venter gave a great opening plenary session, talking about the human genome project. I particularly liked the name of one of his organizations: The Center for the Advancement of Genetics. Would it be off-base to suggest that he knew how cute the abbreviation (TCAG) would be?

JUNE

This molecule will cause much suffering this month and is the target of several multi-million dollar ad campaigns. Can you guess what it is?

Histamine
Synthesized in mast cells from histidine (by removing the terminal carboxyl), histamine is released when mast cells degranulate, classically due to cross-linking of surface IgE but probably in response to other stimuli. As pollen season descends upon us, many of us will be looking for anti-histamines to counteract the biological effects of this release at our local drugstores.

MAY

Measuring this molecule was mention by Dr. Rosenthal in his talk May 1 as an unusual liver function test. If you were there, you know the answer. If you weren’t, can you guess what it is?

MEG-X (Lidocaine metabolite)
Lidocaine is a beta-adrenergic receptor blocker used to treat cardiac arrhythmias. The liver rapidly metabolizes the drug, primarily by removing one of two ethyl groups attached to the nitrogen of a glycine attached to a xylide aromatic core. This produces the molecule shown (mono-ethyl-glycine-xylide). Determining the rate of MEG-X production after intravenous lidocaine administration is an uncommon estimate of liver metabolic function.

APRIL

 

This molecule may have been used to kill Stalin in 1953, according to a new book ("Stalin's Last Crime"). It is a therapeutic drug which is also used in rat poison. Can you guess what it is?

Warfarin
The major derivative of coumarin (a molecule present naturally in sweet clover) is warfarin (one tradename: Coumadin). It inhibits vitamin K reductase, limiting the amount of available reduced vitamin K, an important co-factor for carboxylases that produce clotting factors in the liver. According to the book, Stalin died of a brain hemorrhage (associated with gastric hemorrhage) after an all-night dinner with associates.

MARCH

This molecule occurs naturally in some plants and is available in non-prescription diet aids, one of which was implicated in the recent death of a young baseball player during spring training. Can you guess what it is?

Ephedrine
This sympathomimetic amine is used in nasal decongestants but is also present in many food supplements sold as energizers or weight-loss products. Baltimore Orioles pitcher Steve Bechler (who collapsed and died during spring training last month) was using such a supplement. The effects of ephedrine toxicity are similar to those of amphetamine and may cause sudden death.

FEBRUARY

This molecule comes straight from the heart, despite its name. Can you guess what it is?

 

Pro-BNP (B-type naturietic factor)
Either just before or just after release by the myocardial cell, the molecule is cleaved at the 76-77 peptide bond (shown as a gap just left of the circle at the right). The 77-108 fragment (with the circle) is the active hormone (and is measured by the Biosite BNP assay); the N-terminal 1-76 fragment (called NT-pro-BNP) is measured by the Roche assay. The role of this molecule in diagnosing and monitoring congestive heart failure was the subject of our February meeting.

JANUARY

This molecule was responsible for a number of deaths during a recent terrorist attack. Can you guess what it is?

Fentanyl
It may not look like morphine but fentanyl is an agonist for the same opioid receptor (and has almost 100 times the potency of morphine). It has a shorter duration of action and has been used as an anesthetic. Elderly patients require lower doses which may explain the unexpected number of casualties among the hostages in Moscow when Russian agents used fentanyl to attack terrorists late last year.

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